A 35-year-old man was admitted with fever and right-sided chest pain. A chest X-ray film showed an apple-sized mass shadow in the right lower lobe and minimal pleural effusion Cryptococcus neoformans was identified by culture of the pleural effusion. Transbronchial lung biopsy was done, and pulmonary cryptococcosis was diagnosed. The patient's condition improved after treatment with fluconazole and miconazole. Two months after discharge he was readmitted with a massive ipsilateral pleural effusion. The serum cryptococcal antigen titer was almost normal, and examination of the effusion for cryptococcal antigen was negative. The effusion resolved with thoracic drainage and administration of imipenem. The second effusion was believed to have resulted not from cryptococcosis, but from another bacterial infectin. This case indicates that determination of cryptococcal antigen in serum is useful for diagnosis of pleural effusion and for monitoring pulmonary cryptococcosis. Clinical studies of five patients with pulmonary cryptococcosis indicated that symptoms and abnormal laboratory data were positive only in those with rather large lesions. In all cases the diagnosis was made after transbronchial lung biopsy, and treatment with antifungal agents including fluconazole was successful.