PURPOSE: Although cryptococcosis is a significant opportunistic infection among patients with human immunodeficiency virus (HIV), there is conflicting information on rates of cryptococcosis among HIV-positive and HIV-negative patients. Precise state-wide epidemiologic data for cryptococcosis are not available in Alabama. METHODS: We conducted an active laboratory and hospital medical record-based surveillance for cryptococcosis in Alabama from October 1, 1992 to September 30, 1994. A case of cryptococcosis was defined as a patient's initial episode of cryptococcal disease and based on either a positive culture for C. neoformans from any normally sterile site, a positive latex agglutination serologic test for cryptococcal antigen in CSF or serum, or histopathologic findings consistent with C. neoformans. RESULTS: Over the two year period, 153 cases were identified. The diagnosis was based on positive culture (37%), positive antigen (24%), positive autopsy culture (2%), and histopathologic findings (4%). Further, 33% of the total cases were diagnosed from combined positive culture, antigen, or histopathology. Of the total 153 cases, 55% were in HIV- positive patients and 44% were in HIV-negative individuals and one case (1%) had an unknown HIV status. The overall annual incidence rate of cryptococcosis was 1.89 cases per 100,000 population. The incidence was 1638.7 per 100,000 in the HIV-positive population and 0.84 per 100,000 in the HIV-negative population. CONCLUSION: The first Alabama statewide active surveillance system for cryptococcosis confirms previous observations that rates of cryptococcosis are consistently higher in HIV-infected individuals than in their HIV-negative counterparts. In Alabama, cryptococcosis occurs more commonly in urban residents and in men. Cryptococcosis in HIV-positive persons is more likely to occur in the 20 to 44 year age group, whereas cryptococcosis in HIV-negative persons is more likely to occur in those greater than 45 years old.