A retrospective case controlled study was performed to determine the cost impact of cytomegalovirus disease in the first year following renal transplantation as a basis for the analysis of cost effectiveness of prophylactic and therapeutic regimens directed at CMV infection. Eleven sequential cases of organ-specific CMV disease were matched with 22 controls for age, diabetic status, and donor/recipient CMV serologic status from 119 consecutive first cadaveric renal transplant recipients performed at a single university-affiliated, solid organ transplant unit between January 1, 1988 and March 31, 1990. The groups were comparable for sex, HLA match and mismatch, incidence of initial graft dysfunction, and immunosuppression. Hospitalization data, resource utilization, and costs for all 33 subjects were obtained for a one-year period after transplantation. The mean initial hospitalization time was comparable for both CMV cases and controls (14.5 vs. 15.0 days, P=NS), but patients developing CMV disease averaged 59 hospital days during the first year posttransplant versus 22 days in the control group (P=0.001). A mean of 31 days hospitalization was directly related to CMV disease. Mean total institutional costs, calculated in 1988 Canadian dollars, were 2.5 times higher for patients with CMV disease than for controls ($42,611 vs. $17,309, P=0.001), reflecting predominantly a difference in general ward ($19,988 vs. $7484, P=0.001), hotel ($2508 vs. $927, P=0.001), clinical laboratory ($5420 vs. $2558, P=0.0001), radiology ($1581 vs. $640, P=0.05), and pharmacy ($4916 vs. $1782, P=0.01) costs and utilization. Operating room, special ward, ancillary, and mean per diem costs ($719 vs. $790, P=NS) were not significantly different between the two groups. Functional graft survival at 1 year was 72% in patients with CMV disease compared with 86% in controls, reducing the mean calculated cost-effectiveness of transplantation by 2.9-fold. These data show that CMV disease has significant economic impact on renal transplantation as a result of extended hospitalization. In order to develop a cost effective management approach to CMV infection, this impact must be considered when assessing therapeutic and prophylactic regimens and protocols of organ allocation.