We retrospectively evaluated the clinical manifestations, diagnosis, treatment, and outcome of coccidioidomycosis in 91 patients infected with human immunodeficiency virus (HIV) at a single institution. Coccidioidomycosis was the AIDS-defining illness in 37 patients. Fever and chills, weight loss, and night sweats were the most frequent symptoms. The lung was the most frequently involved organ (80%), followed by the meninges (15%). A diffuse reticulonodular infiltrate was seen in 59 patients (65%), and 13 (14%) had focal pulmonary disease; for 15 patients (16%), the chest radiograph was normal. Coccidioidal serologies were positive for 60 patients (68%), while for 23% with proven coccidioidomycosis such tests were negative Most patients were treated with systemic amphotericin B and then an oral azole. The mortality for the whole group was 60%. Patients with diffuse pulmonary disease had the highest mortality (68%), with a median duration of survival of 54 days (P < .05; 95% confidence interval, 147-175 days). The presence of diffuse pulmonary disease and a CD4 lymphocyte count of < 50/microL were independent predictors of death. In our experience, coccidioidomycosis is an important opportunistic infection that causes substantial morbidity and mortality among HIV-infected patients living in an area of endemicity.