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In November, 1947, a dizzy, sweating Sheila Bennet returns to New York City from Cuba. She checks into a cheap hotel and phones her husband, Matt Krane, who warns her to stay away from their apartment in case it is under surveillance by treasury agents. Unknown to Sheila, Matt is having an affair with her sister Francie and does not want her to discover them together. Feeling increasingly ill, Sheila goes in search of a doctor and, when she collapses on the street, a policeman takes her to a health center. While waiting for a doctor, she talks to Walda Kowalski, a young girl who is there for a checkup. Dr. Ben Wood finds nothing seriously wrong with Sheila, who has given him a false name, and sends her away with some cold medicine. When Sheila then pays Matt a surprise visit, Francie pretends that she is just visiting and, after she leaves, Matt questions Sheila carefully about the stolen diamonds that she sent from Cuba. While he waits anxiously for the package, Sheila continues to grow sicker. At the hospital, Ben is puzzled by Walda's new symptoms, and eventually, identifies her disease as smallpox, a diagnosis that is confirmed when he learns that Walda was never vaccinated against it. Quickly, Ben vaccinates the rest of the hospital staff, and health officers from the New York Department of Health start to vaccinate everyone who might have had contact with the girl. Despite their efforts, one out of three of those who contract the disease die, Walda among them. Now, Ben and his colleagues try to determine how Walda contracted the disease in the first place. Meanwhile, Matt receives the package of diamonds and, leaving Sheila behind, tries to fence the jewels, but is told that he must wait until the hunt for the diamonds dies down. When Sheila figures out Matt's double-cross, she searches for him and continues to spread the disease she is carrying. Sheila learns about Matt's affair with Francie and hurries to her sister's apartment, where she discovers that Francie has killed herself. She then goes to a flophouse that is managed by her brother Sid, stopping at a public drinking fountain on the way. As more and more cases of smallpox develop, the Health Department decides the only solution is to vaccinate the entire city. Meanwhile, treasury agents are pursuing Sheila, whom they believe will lead them to the stolen diamonds. Eventually, the Health Department doctors and the treasury agents realize that they are looking for the same woman. They trace her to Sid's, but he spots the police and helps Sheila escape. When the city runs out of vaccine, the mayor exhorts drug manufacturers to produce more immediately. Then, one night, Sheila appears at the clinic. When Ben tries to get her to stay, she shoots him. He manages to call the police, but Sheila flees to a convent, determined to stay alive until she finds Matt. When Matt returns and murders the fence, he finds Sheila waiting with a gun. She telephones the police, intending to turn him in for the murder of the fence, but collapses before they arrive. Matt tries to escape and falls to his death. Before Sheila dies, Ben questions her about her illness and, using this new information, is able to control the epidemic.