Influenza is caused by a virus that is transmitted from person to person through airborne respiratory secretions. An outbreak can occur if a new strain of influenza virus emerges against which the population has no immunity. The influenza epidemic of 1918–19—which is more precisely called a pandemic because it affected populations throughout the world—resulted from such an occurrence. The cause of the extreme mortality of this pandemic—an estimated 25 million deaths—is not known.

The pandemic occurred in three waves. The first apparently originated during World War I in Camp Funston, Kansas, U.S., in early March 1918. American troops that arrived in western Europe in April are thought to have brought the virus with them, and by July it had spread to Poland. The first wave of influenza was comparatively mild; however, during the summer a more lethal type of disease was recognized, and this form fully emerged in August 1918. Pneumonia often developed quickly, with death usually coming two days after the first indications of the flu. For example, at Camp Devens, Massachusetts, U.S., six days after the first case of influenza was reported, there were 6,674 cases. The third wave of the epidemic occurred in the following winter, and by the spring the virus had run its course. In the two later waves about half the deaths were among 20- to 40-year-olds, an unusual mortality age pattern for influenza.

Outbreaks of the flu occurred in nearly every inhabited part of the world, first in ports, then spreading from city to city along the main transportation routes. India is believed to have suffered at least 12,500,000 deaths during the pandemic. In the United States about 550,000 people died. Altogether an estimated 25,000,000 persons throughout the world perished, most during the brutal second and third waves. Other outbreaks of Spanish influenza occurred in the 1920s, but with declining virulence.