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Following the Spanish-American War of 1898, Yellow Fever rages through Havanna, killing thousands of Cuban civilians and American soldiers. U.S. Army medical corps. surgeon Major Walter Reed and his staff are frustrated in their attempts to stop the disease's spread until Reed learns about an old theory of retired doctor Finlay. Reed visits Finlay and learns that nineteen years before, Finlay had proposed that a mosquito named the stegomia carried the disease. Because his theory was ridiculed, Finlay could not prove its validity and suggests to Reed that he could prove it now. Because the disease does not appear in animals, Reed realizes that he must scientifically test it on humans and decides to ask for volunteers among the soldiers stationed in Cuba. He knows that to prove the theory he must study two groups of men under controlled conditions. Though Reed is offering volunteers $300 each to participate in the experiment, no one comes forward. Nurse Frances Blake, who admires Reed and believes in his work, asks Sgt. John O'Hara, a solider who is in love with her, to volunteer himself, but he refuses to do so and the two quarrel. When Dr. Lester Lazear, one of Reed's staff, dies after being bitten by the mosquito himself, however, Breen a young soldier in O'Hara's platoon, gets the courage to volunteer. O'Hara and the rest of the men soon follow suit and Reed's experiment, which he plans to last twenty-days, begins. In one cottage, three of the men, Breen, "Jellybeans" and Busch, live in squalid conditions, among unwashed utensils and bed clothes used by men who had died of the fever. In the other cottage, O'Hara and Brinkerhoff stay in a scrupulously clean environment, but one of the them is bitten by the mosquito as the experiment starts. After many days, Brinkerhoff, who had been bitten by the mosquito, is the only who contracts the disease. Though the experiment is apparently successful and Brinkerhoff will recover, Reed knows that to be certain that the theory is correct, he must prove that O'Hara did not get the disease because he is simply naturally immune. Though Nurse Blake, who has now come to love O'Hara, begs him not to do so, he volunteers to be bitten by a disease-carrying mosquito. Soon he becomes gravely ill, but, through arduous work, Reed and his staff develop a serum to fight the disease, and O'Hara lives. Now knowing that the mosquito is the carrier of Yellow Fever, Reed's commanding officer, Major General Leonard Wood, orders his men to clean up Havana and its contaminated water supply, breeding grounds for the insect. After ninety days, their efforts are proven successful when no new cases of Yellow Fever are reported. Finally, Nurse Blake proposes to O'Hara and they plan to marry soon.