The use of CMVIG, approved in 1990 for prophylactic administration in seronegative recipients of kidneys from seropositive donors, has been shown to be extremely effective in preventing the considerable morbidity and mortality associated with CMV disease. While the complex interactions between CMV and the immune system, including the effects of immunosuppressive therapy, are still under investigation, passive immunization with CMVIG offers a practical, safe, and cost-effective means of clinical intervention in renal transplant patients known to be at risk for CMV disease. Further clinical studies will need to explore the mechanisms of interaction of CMVIG with reactivation of latent infection and superinfection and with allograft dysfunction and antirejection therapy. Studies that evaluate the use of CMVIG in combination with other pharmacologic and immunologic interventions, both for prevention and treatment of CMV disease, will guide the use of the drug. CMVIG promises to be most helpful in reducing morbidity and mortality in transplant recipients and other particularly at-risk populations such as those who are immunosuppressed iatrogenically.