A 28-year-old male infected with the human immunodeficiency virus (HIV) developed a pleural empyema caused by Cryptococcus neoformans. He responded well to chest-tube drainage and antifungal therapy; he received fluconazole as maintenance therapy for 1 year and has not relapsed. We reviewed the English-language literature on cryptococcal pleural effusions in patients with and without AIDS. Only three other cases of empyema, one of them in an HIV-infected patient, have been reported. A pleural-fluid cryptococcal antigen test was diagnostic in our case and should be included in the diagnostic evaluation of unexplained pleural empyema/effusion in immunocompromised patients. © 1995 by The University of Chicago. All rights reserved.