The epidemiology of human infection with Histoplasma still has many unknown aspects, but the linkage between these organisms and human beings is being elicited gradually through skin-test surveys, studies of cases of disease, and investigation of environmental factors. Skin-test studies reveal that perhaps the prevalence of histoplasmin sensitivity is highest in the United States. Several countries in Central and South America also contain areas of high prevalence. In Africa, highest reactor rates have been found in the western regions, from Liberia to the Congo. In Europe and the eastern Mediterranean zone, histoplasmal infection is uncommon in lifelong residents, although recent studies emphasize the presence of small, localized foci. In southeast Asia, reactor rates to 30% have been found; the disease is being recognized more often than previously. An unknown element is why only a small portion of the apparently millions of infected persons develop clinical disease. Probably an unusually large infecting inoculum is required to produce clinical disease, which most often has accompanied history of exposure to an extremely dusty environment heavily contaminated with bird or bat feces. Much less certain is the origin of infection for the numerous persons who do not develop clinical disease.