The radiographic distribution of Pneumocystis carinii pneumonia was studied in 64 consecutive patients with acquired immunodeficiency syndrome to determine the demographic and clinical factors that might be associated with predominance of the disease in the upper zones of the lungs. Twenty-three patients were receiving monthly prophylaxis with 300 mg of aerosolized pentamidine by means of inhalation; the other 41 were not receiving pentamidine and served as a control group. Parenchymal abnormalities were present in 63 of 64 patients. Pleural effusion and cystic lung lesions were uncommon and did not differ between the two groups. Patients receiving aerosolized pentamidine were more likely than control patients to have disease isolated or predominant in the upper lobes (odds ratio = 3.9, confidence interval = 1.1-14.1). After the possible effects of confounding variables were taken into account, prophylaxis remained a significant risk factor. Age and a previous history of P carinii pneumonia were not significant cofactors. The pattern of deposition or retention of the aerosolized pentamidine could be responsible for the finding of predominant P carinii pneumonia in the upper lobes of the lungs.