OBJECTIVE To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). METHODS A retrospective survey. METHODS Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. METHODS We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). METHODS A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.