A screening procedure was used to select patients on whom further tests for histoplasmosis were indicated. The tests revealed almost 3,400 (7.5%) positive serologic results in a group of 45,000 patients from more than 80 hospitals. Percentages of positive reactions varied with the histoplasmin sensitivity in the area from which the patients were drawn. Evidence is presented to show that at least one-fourth of these patients with positive serologic tests can be proved by adequate cultural procedures to have histoplasmosis, with or without tuberculosis. The seriousness and frequency of the severe type of histoplasmosis makes this a problem of increasing importance to the general practitioner and chest specialist.