Primary cytomegalovirus (CMV) disease can be prevented in renal transplant recipients with the use of either CMV hyperimmune globulin (CMVIg) or acyclovir. Started within 72 hours of transplantation and continued for 16 weeks posttransplant, CMVIg decreases the incidence of primary CMV disease from 60% to 21 %. Acyclovir administered preoperatively and for 3 months thereafter decreases the incidence of CMV disease from 29% to 8% and is the most cost-effective therapy. The effectiveness of these preparations in preventing CMV reinfection or reactivation has not been established. The utility of therapies other than CMVIg or acyclovir for the prevention of CMV disease has not been proven; CMV vaccination is ineffective, polyvalent immunoglobulins require further study, and interferon alpha (IFN-α) has been associated with frequent irreversible rejection reactions and therefore should not be used for CMV prophylaxis. Although further investigation is necessary, patients at risk for primary CMV disease should receive prophylactic therapy with either CMVIg or acyclovir. © 1990, National Kidney Foundation, Inc.. All rights reserved.