Pneumocystis carinii is the pre-eminent pulmonary pathogen and leading cause of death in patients with acquired immunodeficiency syndrome (AIDS). The diagnosis of this organism depends upon the morphologic demonstration of the cyst wall, trophozoite, or sporozoite in specimens from the lower respiratory tract. A variety of histochemical stains have been used to identify P. carinii, each with considerable limitations in specificity. Extrapulmonary spread and unusually destructive pulmonary patterns associated with P. carinii, although once considered rare, are seen occasionally in patients with AIDS. Traditional stains have proven to be less reliable in extrapulmonary sites. In 13 patients with AIDS, we stained formalin-fixed paraffin-embedded autopsy lung and other visceral organ sections using monoclonal antibody 3F6 (Dako, Santa Barbara, CA) to P. carinii. The antibody stained P. carinii in the lungs of seven patients with P. carinii pneumonia by Gomori methenamine silver stain (GMS). Numerous aggregates of P. carinii cysts were marked within alveoli, as is usually seen with other stains. No antibody staining was present in autopsy lung sections from non-AIDS patients with viral, fungal, or bacterial pneumonia. Clinically occult extrapulmonary P. carinii infection was seen in 4/7 (57%) patients with P. carinii pneumonia at autopsy. Monoclonal antibody to P. carinii stained organisms in all four (100%) patients with disseminated disease, as compared with 1/4 (25%) staining with GMS. Antibody staining of P. carinii was demonstrated in sections of thyroid, adrenal, and carinal lymph node (one patient), esophagus (one patient), kidney (one patient), and heart, thyroid, kidney, adrenal, liver, stomach, pancreas, spleen, and bone marrow (one patient).(ABSTRACT TRUNCATED AT 250 WORDS)