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After brawling over a card game in the wharf area of New Orleans, a man named Kochak, suffering visibly from a flu-like illness, is killed by gangster Blackie and his two flunkies, Kochak's cousin Poldi and a man named Fitch. They leave the body on the docks, and later when the dead man, who carries no identification, is brought to the morgue, the coroner grows suspicious about the virus present in his blood and calls his superior, Dr. Clinton Reed, a uniformed doctor working for the U.S. Public Health Service. Reed is enjoying a rare day off with his wife Nancy and their son Tommy, but decides to inspect the body. After careful examination, he determines that Kochak had "pneumonic plague," the pulmonary version of bubonic plague. Reed springs into action, insisting that everyone who came into contact with the body be inoculated. He also orders that the dead man's identity be determined, as well as his comings and goings during the previous few days. Reed meets with people from the mayor's office, the police commissioner and other city officials, but they are skeptical of his claims. Eventually, however, his impassioned pleas convince them that they have forty-eight hours to save New Orleans from the plague. Reed must also convince police captain Warren and the others that the press must not be notified, because report of a plague would spread mass panic. Warren and his men begin to interview Slavic immigrants, as it has been determined that the body may be of Armenian, Czech or mixed blood. Burdened by the knowledge that the massive investigation has little chance of success, Reed accuses Warren of not taking the threat seriously enough. In turn, Warren admits that he thinks Reed is ambitious and trying to use the situation to further his career. Reed, angry, decides to take matters into his own hands and, acting on a hunch that the man may have entered the city's port illegally, goes to the National Maritime Union hiring hall and passes out copies of the dead man's picture. Although the workers tell Reed that seamen never talk, he goes to a café next door hoping that someone will meet him with a tip. Eventually a young woman shows up and takes Reed to see her friend Charlie, who reluctantly admits that he worked aboard the ship, the Nile Queen , upon which the already ill man was smuggled. Meanwhile, Fitch, who was questioned by Warren but claimed to know nothing, goes to Blackie and warns him about the investigation. Blackie plans to get out of town, but begins to suspect that his sidekick Poldi received expensive smuggled goods from Kochak, explaining the police's intense investigation of the man's murder. Reed and Warren, who is now convinced of Reed's integrity, go to the Nile Queen and convince the crew to talk by telling them that they will die if the sick man was indeed on their ship. After carrying up a sick cook from the hold, the seamen then permit Reed and Warren to inoculate and question them, revealing in the process that Kochak boarded at Oran and was fond of shish-kebob. With this lead, Reed and Warren canvas the city's Greek restaurants, and just after they leave one such establishment, Blackie arrives to meet Poldi, who is very ill. A short time later, Reed receives word that a woman, Rita, has died of the fever and realizes that she was the wife of the Greek restaurant proprietor who had earlier lied about having served Kochak. Reed returns to headquarters to discover that a reporter is threatening to break the story that a virus is endangering the city. Reed is impressed when the deeply committed yet unorthodox Warren throws the reporter into jail to keep him quiet. Late in the evening, a beleaguered Reed returns home for a few hours of sleep, and his wife announces that she is pregnant. She then tries to restore her husband's flagging self-confidence. A few hours later, Reed and Warren learn that the mayor is angry about their treatment of the reporter. The reporter, who has been released, announces that the story will appear in the morning paper in four hours, giving Reed and Warren little time to find their man. Meanwhile, Blackie goes to Poldi's room and tries to force him to reveal information about some smuggled goods, but the dying Poldi is delirious and only rants nonsensically. Blackie then brings in his own doctor and tells Poldi's grandmother that they will take care of him. Just then, Reed, having been tipped off by the Greek restaurant owner, arrives, and Blackie and Fitch, who are carrying Poldi down the stairs, pitch the man over the side and flee. Reed chases the two to the docks, where he tries to explain to them about the plague. The men run desperately through depots, docks and a warehouse, and at one point, Warren shoots and injures Blackie, preventing him from shooting Reed. Blackie accidentally shoots Fitch and then tries to struggle onto a ship but, exhausted, falls into the water. His work finally done, Reed heads for home, and on the way, Warren offers to give him some of the smuggled perfume that Poldi had indeed received from Kochak. As the radio announces the resolution of the crisis, a proud Nancy greets her husband.