Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) is routinely given after allogeneic blood or marrow transplantation. We evaluated the effectiveness of dapsone prophylaxis (50 mg orally twice daily, 3 times per week) compared with twice-weekly trimethoprim-sulfamethoxazole (TMP-SMZ) in preventing PCP after allogeneic blood or marrow transplantation. Patients included all (n=646) who received allogeneic blood or marrow transplants between 1 September 1993 and 31 December 1996 who survived at least 100 days after transplantation. A cohort of 111 dapsone recipients was compared with the remaining 535 who received TMP-SMZ. Ten patients developed PCP; 8 were taking dapsone. PCP incidence in the TMP-SMZ cohort was 0.37% versus 7.2% for dapsone. The relative risk for PCP associated with dapsone use was 18.8 (P<.001) and was not accounted for by age, clinical extensive chronic graft-versus-host disease, donor source, or malignant relapse. Dapsone prophylaxis at this dosage is associated with significantly higher rates of PCP than is TMP-SMZ after allogeneic marrow transplantation. We advise caution in prescribing alternatives to TMP-SMZ prophylaxis in this setting.