Cryptococcosis is a common opportunistic infection in patients with AIDS. Meningitis is the most frequent manifestation of infection with Cryptococcus neoformans; pneumonia due to this organism, though less frequently recognized, is also a significant entity. A retrospective review was performed of all patients seen at Duke University Medical Center between January 1981 and July 1989 who were infected with both human immunodeficiency virus type 1 and C. neoformans. Of 31 patients with these concomitant infections, 12 had cryptococcal pneumonia (10 definite and two presumptive cases). Eleven of these 12 patients had evidence of extrapulmonary cryptococcal disease as well. Chest radiography showed interstitial infiltrates in 11 instances. For ten of the 12 patients, pulmonary cultures were positive for C. neoformans. Bronchoalveolar lavage fluid from all five patients who underwent bronchoscopy yielded the organism. Acute-phase mortality from cryptococcosis was 42% among patients with pneumonia. Cryptococcal pneumonia in patients with AIDS is probably more common than has previously been recognized and typically presents as interstitial disease that may mimic other opportunistic infections.