Forty-two cytomegalovlrus (CMV)-seropositive allogeneic marrow transplant patients or recipients of CMV-seropositive marrow allografts were entered Into a surveillance program to detect and treat CMV Infection during the first 120 days posttransplant. CMV Infection was detected at a mean time of day 50 In 21/37 (58%) patients who had surveillance cultures. Twelve of 42 (28%) received preemptive ganclclovir treatment for virus isolated from blood (9 patients) or from bronchoalveolar lavage fluid (3 patients), and all had no CMV-associated sequeiae. CMV disease was diagnosed In 5 patients (4 with pneumonia, 1 with gastroenteritis) who did not have positive cultures until the onset of their disease. CMV-related mortality was 4/42 (10%). Patients who earlier manifested lung Injury or diffuse alveolar hemorrhage (DAH) were significantly predisposed to subsequent CMV pneumonia (P = 0.0013, Fisher's exact test) at a median onset of day 42. Restricted prophylactic use of ganclclovir in such patients may be indicated. Fifty percent of all patients never required ganciclovir during the surveillance period. When compared to a universal prophylaxis program of ganciclovir for the prevention of CMV disease, the use of ganclclovir in a preemptive strategy could avoid unnecessary therapy for a substantial number of patients and earn significant cost-savings.