OBJECTIVE To describe the epidemiology and pathogenesis of cytomegalovirus (CMV) and critically analyze the studies evaluating the cost, safety, and efficacy of high-dose acyclovir, intravenous immune globulin (IVIG), and CMV hyperimmunoglobulin (CMVIG) for prophylaxis against CMV in kidney transplant recipients. METHODS Appropriate articles were identified by searching MEDLINE. Various combinations of the following medical subject heading terms were used: immunoglobulins, intravenous; acyclovir; CMVIG; CMV infections; kidney transplantation; IVIG; and prophylaxis. METHODS Studies evaluating or discussing the cost, safety, and efficacy of IVIG, high-dose acyclovir, and CMVIG in kidney transplant recipients were included. METHODS The data were evaluated with respect to study design, patient population, prophylactic regimen, incidence of CMV complications, investigators' definitions of terminology, and cost analysis. The studies are summarized in tables and discussed in the text. RESULTS The definitions of terminology used by the investigators varied widely among studies. The studies were reviewed and discussed using the following definitions: CMV infection was the presence of CMV antibodies in a previously CMV-seronegative patient or a fourfold rise in antibody titer after transplantation; CMV syndrome was CMV infection plus unexplained fever, leukopenia, or thrombocytopenia in the absence of an identifiable cause; and CMV disease was CMV syndrome plus pneumonitis, enteritis, retinitis, hepatitis, or central nervous system involvement. CONCLUSIONS All regimens appear to effectively reduce the incidence of CMV-associated complications compared with placebo. Due to the lack of trials comparing cost, efficacy, and safety, the most effective prophylactic treatment is unknown.