As a tour bus approaches Hanauma Bay, we see a man (Allan Tan) slumped over a picnic table. He looks very ill. At the bottom of the hill, the bus stops and tourists get out. The man gets up and approaches two of the tourists, but he collapses. Someone riding a motorcycle who is wearing a helmet and a visor approaches the man and takes his billfold out of his shirt pocket. One of the tourists wants to help the man, but the motorcyclist pulls out a gun and the tourist backs off. The person on the motorcycle leaves the scene. The sick man gets up and tries to hold on to a nearby stone wall, but he collapses again.
Doc's examination of the sick man determines that he has bubonic plague. The M.E. says he hasn't seen a "rare specimen" like this in 25 years of practice. There is concern that an epidemic could sweep the islands. People on the bus have already been inoculated.
Outside the man's isolated room in the hospital, McGarrett tries to get information out of him, even getting Chin Ho to speak to the man in Chinese, but the man soon dies. Back at Hanauma Bay, HPD has located the dead man's car. The car's registration reveals him to be Harvey Fong, age 42, a photographer. When Danno and Chin go to Fong's place and search it, they are wearing hazmat-type suits. Someone phones the place while they are there and Danno answers, but the man at the other end of the line, the guy who drove the motorcycle, hangs up.
The Governor sets up a meeting with the Public Health Service, FBI, HPD, Immigration and military. Dr. Alexandra Kemp of Public Health (Nancy Kovak), an attractive blonde, briefs the people present on how the disease is contracted and transmitted and how it is treated. When McGarrett arrives late to the meeting, he asks Kemp if chloramphenicol or chlortetracycline, which was discovered at Fong's, are effective against the plague. She compliments him on being "well informed," but says the drug of choice is streptomycin. McGarrett leers at her, but she ignores him.
The Governor tells people that their problem is twofold: One, treatment. "We must alert the public to the danger without inciting a panic." And two, prevention. Kemp says that whoever lifted Fong's billfold is in danger of getting the disease, and the results will likely be fatal.
Chin Ho gets inoculated against the plague, which causes Kono and Danno to ridicule his reaction to the needle. But then the other two men also are forced to get shots, and Chin has a good laugh at their squirming.
Kemp goes on TV to warn the public, but she doesn't use the word "plague," instead saying the disease is a "form of Asian flu."
A man named Jardine (Herb Jeffries) is watching this broadcast, and is interrupted by his son Kim (George "Keoki" Awai) who was awakened by someone pounding on the door of their neighbor, Mr. Chew. When Jardine goes outside to investigate, he is almost run over by the man on the motorcycle. Going into Chew's house, he finds his neighbor dead.
Jardine says he did not know Chew well when McGarrett shows up at his house, but his son used to run errands for their neighbor.
Chew was a janitor at the Hawaii Institute of Technology. After Jardine and his son are taken to the hospital to get vaccinated, McGarrett visits them there. He finds out that Chew sent Kim to pick up a message at his workplace, but Kim never completed the job. McGarrett and Kim go there to find a note stuck into a parking lot gatepost with a twist-off cap which Kim could not open.
McGarrett meets with army Colonel Tyler (Ed Sheehan) plus two professors, Foley (Norman Wright) and Lasham, regarding this note. They are disturbed to hear the expression "Canebrake," which refers to a night-sight detector under development, which is a major breakthrough in infrared sensory perception. It will pick up a warm body signal of a tomcat at a hundred yards in a pitch-black jungle – like in Vietnam. Every specification of this device is top secret.
Kono has been working the docks, and has found out 11 ships from plague centers have arrived in port in the last two weeks. One of these, the Cap Solidado, is under quarantine, and no one is allowed aboard. A man named Horace Sibley was one of the passengers who disembarked before the quarantine. Danno has tracked down a prescription for both chloramphenicol and chlortetracycline written by a Doctor Leo Kuh (Victor Sen Yung) which was delivered to a house owned by Shen Yu-Lan (David Opatoshu).
When they arrive at this place, they are greeted by Lewis Shen (Soon-Tek Oh). Shen Yu-Lan is Lewis's uncle, an old patriarchal type. McGarrett get only a few minutes to interview the uncle, who says he knows nothing about Fong, despite the fact the prescription was delivered to his house.
Doctor Kuh who wrote the prescription is later tracked down. He says he has 14 patients in Shen Yu-Lan's house, "All relatives, and patients. You could say I'm the resident doctor. I live there. Mr. Shen is my grandfather." He says this prescription was written for the cook who had "carbuncles … in a very delicate area," and laughs.
Tompkins, an artist is painting a picture of an ocean scene in the middle of nowhere. The mysterious motorcycle guy shows up nearby and pushes his bike over a cliff. When Tompkins protests – "That was a terrible waste, man. You could have sold it. Or even given it to me" -- he is shot by the motorcycle guy who removes his helmet, revealing him to be Lewis Shen.
In his office, McGarrett speculates that "Chew was the cutout [an intermediary in a clandestine operation, according to m-w.com]. He's dead." Fong was "part of the espionage network" and "The man on the motorcycle is probably the end of the line." Horace Sibley (Jackie Coogan) comes to the office for an interview. He says he is an importer of Oriental art objects, mostly from Hong Kong. McGarrett tells Sibley that the ship he returned on, the Cap Solidado, is currently under quarantine, and he might be infected with the plague. Sibley says that he was only passenger returning on the boat to Hawaii. McGarrett tells Sibley that it is fishy that in the last year, he has made six trips between Hawaii and Hong Kong, but Sibley tells him to get lost and starts to leaves, threatening to sue for invasion of privacy. McGarrett orders him held because he is a potential plague carrier.
A young woman, Amy Soo (Hai Luen Corragio), also infected with the plague, collapses after she mails a couple of letters in Honolulu. She is taken to the hospital where Dr. Kemp treats her. The woman – who will survive -- tells Kemp a story about how she escaped from China with her fiancé in a rat-infested junk where she likely contracted the disease and then transferred to a freighter. Each was locked in a cargo case with just enough food and water. When they docked in Hawaii and they brought her up from the hold, she was told her fiancé had left the ship. Kemp relates all this to McGarrett.
Danno arrives at the hospital and tells McGarrett about Tompkins, the artist, who was shot and later died, and that the motorcycle was recovered nearby. McGarrett speculates this is connected to the missing fiancé.
When Kemp gets the name of the fiancé from Soo shortly after this, it is Shen Lu, which is sort of the opposite of "Lewis Shen."
At Shen Yu-Lan's house, the old man has received one of the letters which Soo mailed before she passed out. He reads this to his "nephew" Lewis: "I could hear the water against the bottom, and rats scurrying past in the blackness. I crouched in the cargo box, blind as a creature who lives below ground. Day after day, I waited for the ship to reach Hawaii, and when it did, Shen Lew had already gone ashore. Now, honorable uncle of my fiancé, I am at last in Honolulu, but alone and sick."
The old man is annoyed because his nephew said nothing about this woman. Lewis says he will check the hospitals to see if he can help.
McGarrett confronts Shipley in his office once again, accusing him of smuggling Soo and her husband-to-be into the islands for money, a story which Soo confirmed in the hospital. Her family paid Shipley $25,000 to bring her to the States, a typical rate which he charges, based on deposits into his multiple bank accounts.
McGarrett and Danno go to visit Shen Yu-Lan. They tell him they suspect his "nephew" is really an imposter, a Chinese agent who murdered his real nephew at sea. As well, the imposter picked up the plague from the real nephew. The old man goes to confront Lewis, who is in another part of the house, about his deception. Lewis shoots him dead.
Colonel Tyler contacts McGarrett, saying that they caught the man at their end who was dealing with the Red Chinese. Tyler tells McGarrett that the Canebrake device is "in a chopper on its way to the testing site," but at almost the same moment, the Colonel gets another phone call saying that the helicopter carrying it has crashed. McGarrett hurries to the scene, where Tyler confirms the crash was the result of sabotage, and that now Shen Lew has got the device.
Meanwhile, at the hospital, a man (Arthur Hee) has walked in and said he wants to be treated for "the plague" which "some fellow" said that he might have. It turns out that he rented a room in his garage to this "fellow," who just happens to be Lewis Shen. At the man's garage, McGarrett and Danno find the Canebrake machine, figuring that Shen has already taken it apart and made a schematic of the insides.
McGarrett and Danno then go to see Doctor Kuh, telling him that Lewis Shen murdered his uncle (actually his grandfather). As well, "He brought a plague to these islands that you concealed. As a doctor, the responsibility for that lies on your doorstep. Now it's up to you."
Shen prepares to leave the country on a fishing boat. Chin Ho is nearby on the docks, and McGarrett and Danno are close by. While trying to arrest Shen, Chin gets shot in the arm, and when Shen attempts to escape, McGarrett boxes him in with his car. Shen is wounded and almost takes a cynanide pill. McGarrett tells him "No chance. We got some talking to do, and I want some answers."
Shen is taken away. Chin Ho will recover.