To measure the incidence in the United States of systemic mycoses necessitating hospitalization, we reviewed discharge records of 1,875 hospitals participating in the Professional Activity Study of the Commission on Professional and Hospital Activities. Projected incidence rates in 1976 ranged from 23.0 per million for histoplasmosis to 0.2 per million for blastomycosis. High prevalences of leukemia or lymphoma (5.9% to 10.2%) or of other malignancies (9.9% to 13.2%) were recorded in patients with aspergillosis, candidasis, or cryptococcosis. High prevalences of chronic obstructive lung disease (9.6% to 9.9%) were recorded in those with aspergillosis or histoplasmosis. Marked increases from 1970 to 1976 were found in the incidence of aspergillosis (158%), actinomycosis (92%), cryptococcosis (78%), and coccidioidomycosis (74%). Increasing numbers of persons with immunosuppressive conditions, migration of susceptible persons into hyperendemic areas, and aging of the population contributed to the increases.