Cytomegalovirus (CMV) is an important cause of morbidity, mortality and cost in cadaveric renal transplantation. This study was designed to document the clinical and economic outcomes associated with donor and recipient CMV sero-pairing. Data were drawn from the United States Renal Data System (USRDS) on 17 001 cadaveric renal transplant recipients transplanted between 1995 and 1997 with recorded donor and recipient CMV sero-status. In multivariate analysis, CMV-seropositive recipients were associated with a significantly higher incidence of delayed graft function, a lower incidence of graft loss, and lower costs than CMV-seronegative recipients. CMV-seropositive compared to seronegative donors were associated with significantly higher incidence of CMV disease, graft loss, and higher costs when transplanted into CMV-seronegative recipients. However, CMV-seronegative donors into seropositive recipients had no significant association with outcome beyond a higher incidence of CMV disease compared to CMV-seronegative donor and recipient pairs. The outcomes associated with CMV-seropositive donors and seronegative recipients call for tailored management strategies which may include avoidance of such mismatching, antiviral therapy, immunization, or modified immunosuppression.