At the end of the 19th cent., yellow fever was highly prevalent in the Caribbean, and a way of controlling it had to be found before construction of the Panama Canal could be undertaken. In 1900 an American commission headed by Walter Reed and including James Carroll, Jesse Lazear, and Arístides Agramonte gathered in the U.S. Army's Camp Columbia in Cuba. Through their experiments—one of which severely sickened Carroll and killed Lazear—they proved the theory of C. J. Finlay that yellow fever was a mosquito-borne infection. Within the next few years, W. C. Gorgas, an army physician and sanitation expert, succeeded in controlling the disease in the Panama Canal Zone and other areas in that part of the world by mosquito-eradication measures. The later development of an immunizing vaccine (work on which won Max Theiler a Nobel Prize) and strict quarantine measures against ships, planes, and passengers coming from known or suspected yellow-fever areas further aided control of the disease.

Yellow fever begins suddenly after an incubation period of three to five days. In mild cases only fever and headache may be present. The severe form of the disease commences with fever, chills, bleeding into the skin, rapid heartbeat, headache, back pains, and extreme prostration. Nausea, vomiting, and constipation are common. Jaundice usually appears on the second or third day. After the third day the symptoms recede, only to return with increased severity in the final stage, during which there is a marked tendency to hemorrhage internally; the characteristic "coffee ground" vomitus contains blood. The patient then lapses into delirium and coma, often followed by death. During epidemics the fatality rate was often as high as 85%. Although the disease still occurs, it is usually confined to sporadic outbreaks.