In this true story based on a play by Sidney Howard and Paul de Kruif, Dr. Walter Reed conducts experiments to learn the cause of yellow fever.
In Cuba in 1900 Major Walter Reed (Lewis Stone) and Dr. James Carroll (Stanley Ridges) admit they don't understand yellow fever. Soldiers Jellybeans (Buddy Ebsen) and Busch (Sam Levene) complain they remain after the war. Sergeant John O'Hara (Robert Montgomery) carries a soldier with yellow jack into the hospital so he can talk with nurse Frances Blake (Virginia Bruce). Reed refuses to quit. O'Hara says the victim had been in the guardhouse with eight men for a month. Breen (William Henry) worries about germs. Frances tells O'Hara she wants to help the doctors. Reed goes to the guardhouse, sees it is sanitary, and suspects insects. He learns that Dr. Finlay (Charles Coburn) believes it is caused by a mosquito. Finlay says that only a human experiment can prove his theory, and he gives Reed mosquito eggs. General Wood (Jonathan Hale) calls in Major Gorgas (Henry O'Neill), who says the Panama canal is delayed by yellow fever. Reed gets permission to use soldiers, and volunteers are offered $300.
Dr. Carroll says he had himself bitten eight days ago, because no one has volunteered. Dr. Jesse Lazear (Henry Hull) is bitten by a mosquito by mistake. Frances sends Charlie Spill (Andy Devine) so she can meet O'Hara. O'Hara's men dig a grave and discuss volunteering. Charlie tells O'Hara that he persuaded Frances to meet him. By a lake Frances asks O'Hara why no one volunteered and says how Reed needs just one; but O'Hara gets angry. Breen tells O'Hara that Lazear got yellow jack, and he dies. Breen faints and says he wanted to volunteer but couldn't. O'Hara tells Reed that he Breen, Busch, Jellybeans, and Brinkerhof (Alan Curtis) are volunteering for no money. Reed puts three men in a dirty tent with contaminated clothes. Breen volunteers to be bitten in a clean room, and O'Hara lives with him. Frances thanks O'Hara.
After five days Breen gets fever. Reed explains that O'Hara may be immune, and a mosquito bite will prove if he is. O'Hara agrees. The other three men are miserable but healthy. O'Hara is bit by several mosquitoes and gets the fever. O'Hara is delirious, but Breen is recovering. Gorgas orders all exposed water in Cuba removed. Jellybeans, Busch, and Brinkerhof get out and join the troops pouring out the water, where mosquitoes breed. The colonel reports to Gen. Wood that after 90 days no cases of yellow fever exist in Cuba for the first time. O'Hara tells Frances he is going to Panama to help Gorgas, but she asks him to come to Washington with her. O'Hara asks her to marry and marches off. An epilog commemorates the names of the five volunteers.
This remarkable film uses the names of the actual doctors who solved this long-standing scourge that had taken so many human lives. The fictionalized personal lives of the volunteers add charm and humility to a heroic and historic story.