Pneumonia unresponsive to antibacterial agents in patients with acquired immune deficiency syndrome (AIDS) has become a new indication for lung biopsy. In 14 patients, transbronchial or open-lung biopsy demonstrated Pneumocystis carinii. An additional 12 patients, who were immunosuppressed after renal transplantation, were seen with P. carinii pneumonia. The diagnosis was established by transbronchial biopsy in the majority of patients. All patients were treated initially with trimethoprim plus sulfamethoxazole. Pentamidine was added after diagnosis if improvement did not occur. Both groups demonstrated reversal in the T cell helper: suppressor ratio. We compared these two groups of immunocompromised patients with respect to clinical presentation, lung pathology, response to therapy, and survival. Patients with AIDS were seen with a two- to three-week prodrome of fever, lymphadenopathy, weight loss, and malaise followed by hypoxia and leukopenia within 12 hours. Transplant patients became acutely ill with fever and hypoxia within 24 to 36 hours. In both groups, chest roentgenogram showed bilateral diffuse infiltrates; sputum cultures were generally negative; and lung biopsy demonstrated Gomori-Jones periodic acid-methenamine-silver-positive P. carinii. Mortality was substantially higher in patients with AIDS (50% versus 8%). This difference may be explained by the fact that the T cell defect in AIDS has an infectious cause, while the defect in the renal allograft recipient is pharmacologically mediated.