Most series of heart transplant patients report incidences of Pneumocystis carinii pneumonia (PCP) below 5% but do not individually describe the cases. From August 1988 to March 1994, 138 patients received 1 or more heart transplants at our institution. No anti-PCP chemoprophylaxis was provided, and 5 (3.6%) patients developed PCP. Incidence for listeriosis was 0.7% and for nocardiosis, 3.6%. We found descriptions of 14 more heart transplant patients with PCP in the medical literature. Data from the 19 patients follow. Mean age was 52 years, and PCP was diagnosed a median of 75 days after heart transplant (range, 37-781 d). Clinical presentation was acute (less than 48 h) with fever (89%), shortness of breath (84%), dry cough (74%), and hypoxia (63%). Cytomegalovirus was isolated from lung or blood in 74% of patients. Chest X-ray usually showed interstitial pneumonia (84%). Three patients required ventilatory support. All patients were treated with trimethoprim-sulfamethoxazole (TMP/SMX) (4 also with corticosteroids and 5 with ganciclovir). Mortality was 26%. Older age was the only significant poor prognostic factor (61 versus 49 years; p < 0.03). From March 1994, 50 heart transplant patients were given TMP/SMX prophylaxis at our institution (1 double-strength tablet, 160/800 mg, every 12 hours on Saturdays and Sundays), and no new cases of PCP, Listeria or Nocardia have been detected since then. Tolerance has been excellent. Heart transplant recipients are at a substantial risk of PCP pneumonia, which presents with an abrupt onset and a high mortality. Weekend TMP/SMX chemoprophylaxis was very effective at our institution.