OBJECTIVE To determine the incidence and factors associated with extrapulmonary cryptococcosis among a cohort of persons with HIV in Los Angeles County. METHODS Records-based cohort study. METHODS Data were analysed from a cohort of 3836 persons aged > or = 13 years with HIV infection enrolled from four outpatient facilities in Los Angeles from 1990 to 1995. The potential association between cryptococcosis and demographic risk behavior and clinical factors was assessed. Possible seasonal clustering was evaluated and an estimate of survival following cryptococcosis was calculated. Multivariate analysis was performed using a Cox proportional hazards approach. RESULTS Cryptococcosis was identified in 112 patients (2.9%) representing a crude incidence rate of 1.7 cases per 100 person-years experience. The rate of cryptococcosis was higher among men than women (1.9 and 0.6, respectively; P < 0.01) and in Hispanics than in whites (2.3 and 1.2, respectively, P < 0.01). A significant trend of decreasing cryptococcosis was observed with increasing age (P < 0.01). Cryptococcosis increased with declining CD4+ lymphocyte count, with risk being greatest at CD4+ cell counts below 100 x 10(6)/l (P < 0.001). In bivariate analysis persons with a history of antifungal medication had a marginally lower rate of cryptococcosis, but this difference was not statistically significant. The rate of cryptococcosis was significantly higher in fall and winter months [rate ratio (RR), 1.45; 95% confidence interval (CI), 1.0-2.3; P = 0.05]. After controlling for other variables, cryptococcosis was more common in men than women (adjusted RR, 3.2; 95% CI, 1.0-10.4) and in Hispanics than whites (adjusted RR, 1.6; 95% CI, 0.9-2.7). Both CD4+ count and age continued to be strongly associated with the occurrence of cryptococcosis. After controlling for other factors a substantial protective effect was observed for antifungal therapy (adjusted RR, 0.48; 95% CI, 0.29-0.79). CONCLUSIONS Our data suggest that HIV-infected men, Hispanics, persons aged under 45 years and those with CD4+ counts under 100 x 10(6)/l have an increased risk of extrapulmonary cryptococcosis. A fall-winter seasonality in the occurrence of cryptococcosis may exist. Significant primary protection against cryptococcal disease is afforded by antifungal therapy. These results may provide insight into possible routes of transmission and sources of cryptococcal infection and help guide both primary prophylaxis and early recognition and diagnosis in persons likely to be at increased risk.