Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P≤0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival. (N Engl J Med 1988; 318:70–5.) CYTOMEGALOVIRUS infection remains an important obstacle to the success of allogeneic marrow transplantation.1 2 3 In approximately one third of marrow-transplant recipients in whom cytomegalovirus infection develops, the infection will progress to cytomegalovirus pneumonia, with an 85 percent mortality rate.2 Antiviral agents available at present have had little efficacy in the treatment of cytomegalovirus infection after marrow transplantation.4 5 6 7 8 An exception may be the acyclovir derivative ganciclovir, which substantially decreased replication of cytomegalovirus in marrow-transplant recipients with cytomegalovirus pneumonia.9,10 However, survival was not improved. Phosphonoformate (foscarnet) appears to have similar antiviral effects.11 With the exception of the use of screened seronegative blood products.