Clinical and experimental studies have established the accelerating role of cytomegalovirus (CMV) infection on cardiac allograft arteriosclerosis, i.e. chronic rejection. In this study, we investigated the effect of ganciclovir prophylaxis on the development of CMV-enhanced allograft arteriosclerosis. Rat aortic allografts were done from DA donors to WF recipients and either infected with 10(5) plaque-forming units of rat CMV (RCMV) 1 day after transplantation or left uninfected. RCMV-infected allografts received ganciclovir at an initial dose of 20 mg/kg and a maintenance dose of 10 mg/kg twice a day for 14 days. Grafts were removed at 7, 14 days, and 1 and 3 months after transplantation and processed for morphometry and autoradiography. The results of this study demonstrated that ganciclovir prophylaxis significantly delays and reduces RCMV-enhanced allograft arteriosclerosis in the rat.