Over 14 yr 41 patients were diagnosed as having pulmonary cryptococcosis. Cryptococcus neoformans remained localized to the lung in 12 cases and disseminated in the remaining 29. Thirty-four patients were compromised hosts. Disseminated disease developed in 28 of these 34; 4 of these 28 patients with disseminated disease presented with concomitant pulmonary and meningeal infections. In all the remaining 24 CNS involvement developed 2-20 wk after the finding of an abnormal chest roentgenogram. Seven patients were normal hosts; in 6 of these cases disease remained localized to the lung. Pulmonary cryptococcosis is seemingly rarely considered in the differential diagnosis of an abnormal chest differential diagnosis of an abnormal chest roentgenogram, thereby leading to missed diagnoses and therapeutic errors. The natural history of untreated pulmonary cryptococcosis in compromised hosts is evidently extrapulmonic dissemination. Compromised hosts with pulmonary cryptococcosis probably should receive antifungal therapy because of a high propensity for dissemination; normal hosts in whom dissemination has been excluded generally do not need antifungal therapy.