We studied the efficacy and safety of a risk-adapted approach with ganciclovir to prevent cytomegalovirus (CMV) pneumonia in 41 CMV-seropositive recipients of genotypically human leukocyte antigen-identical bone marrow transplants. Prophylaxis with ganciclovir, at a dosage of 2.5 mg/kg twice a day for 14 days, was started when patients were treated with high-dose steroids for acute graft-versus-host disease (i.e., they were considered at high risk for CMV pneumonia), or the drug was given as preemptive therapy when CMV antigenemia developed (i.e., the patients were considered at intermediate risk for CMV pneumonia). Twelve patients (29%) were treated prophylactically and seven patients (17%) preemptively. Only five patients (26%) received a second course of ganciclovir (given preemptively to four patients). Twenty-two patients (54%) never received ganciclovir because they did not fall within these risk groups. None of the 41 patients developed CMV pneumonia. Ganciclovir-related granulocytopenia did not occur (course 1) or was very mild (course 2). We conclude that this approach appears to prevent the development of CMV pneumonia after bone marrow transplantation.