Pleural effusions due to Cryptococcus neoformans occurred in 2 patients, 1 with localized pulmonary infection and 1 with disseminated cryptococcosis. Cryptococcal antigen was present in the pleural fluid from both patients and it was present also in the serum and cerebrospinal fluid of the patient with disseminated infection. The cryptococcal antigen test is a sensitive and specific indicator of cryptococcoal infection, and it was not positive in pleural fluid samples from a variety of other conditions including bacterial and mycobacterial infections and primary or metastatic malignancies. Twenty-eight additional cases of cryptococcal pleural effusions have been reported in the English literature, equally divided between patients with infection localized to the thorax and those with disseminated disease. Cryptococcal infection must be considered in the differential diagnosis of patiients with pleural effusion, especially patients with serious underlying diseases treated with corticosteroids. The cryptococcal antigen test appears to be a useful adjunct in diagnosis, and serial determinations may be helpful in assessing response to treatment.