We performed a prospective study of infections following bone marrow transplantation in 50 patients treated for aplastic anemia or hematologic malignancy. Early, continuous prophylaxis with trimethoprim/sulfamethoxazole and oral nystatin, and empiric intravenous antimicrobial therapy during febrile granulocytopenic episodes were standard treatment for all patients. The use of trimethoprim/sulfamethoxazole did not appear to adversely affect donor marrow engraftment. Serious gram-negative bacillary and systemic Candida infections were uncommon. Although gram-positive bacterial infections were frequent, they were rarely associated with mortality. Aspergillosis emerged as the single most important infection, contributing to the death of nine patients. Cytomegalovirus diseases developed in 13 patients, seven of whom died. Patient age and chronic myelogenous leukemia were risk factors for the development of fatal infections. This study demonstrates that although certain serious infections can be controlled, there is a critical need for effective measures to prevent and treat aspergillosis and cytomegalovirus disease in these seriously compromised hosts.