To examine the clinical manifestations, treatment, and outcome of pulmonary cryptococcosis, we reviewed the medical records of all patients treated for Cryptococcus neoformans infection at our hospital from January 1988 through September 1998. Sixty-three patients were included in the analysis, 10 (16%) of whom had acquired immunodeficiency syndrome (AIDS). Thirty-four of the 53 non-AIDS patients, including 19 men and 15 women had pulmonary cryptococcosis, including 31 with isolated pulmonary cryptococcosis and three with disseminated disease. Of the 10 AIDS patients, seven presented with disseminated cryptococcosis (including one patient with lung involvement) and one had isolated cryptococcal lung disease. The age (mean +/- SD) of the 34 non-AIDS patients with pulmonary cryptococcosis was 52.1 +/- 15.2 years (range, 19-75 yr). Cough was the most common symptom (58%). Diabetes mellitus (12%) and malignancy (12%) were two major underlying diseases. Nodules and masses were the predominant manifestations of pulmonary cryptococcosis in non-AIDS patients (79%). The most frequently used diagnostic modality for pulmonary cryptococcosis was biopsy with/without aspiration under ultrasound guidance (56%). Antifungal therapy (20/34) was the most common treatment for non-AIDS patients, followed by surgical resections with antifungal therapy (9), surgical resections alone (3), and no treatment (2). Antifungal therapy and/or resection yielded excellent outcomes (total recovery, 27; improvement, 4). Of the 18 patients who underwent lumbar puncture, only two had positive cerebrospinal fluid (CSF) cultures for C. neoformans, both had symptoms and signs of increased intracranial pressure. There was no clinical evidence of meningitis in the other 32 patients. Our findings indicate that pulmonary cryptococcosis in non-AIDS patients tends to be a more localized and benign process than in AIDS patients. Ultrasound-guided lung biopsy or aspiration is an effective tool for diagnosis. CSF examination may not be mandatory as an initial routine procedure for pulmonary cryptococcosis in non-AIDS patients.