This study was designed to determine the effect of short-course cyclosporin A therapy (10 mg/kg daily for 14 days) on allograft valve survival across the histocompatibility barriers in the following rat models; (1) syngeneic Lewis to Lewis (herein referred to as autografts), (2) weakly allogeneic AS to Lewis (RT1 compatible, non-RT1-incompatible), and (3) strongly allogeneic CAP to Lewis (RT1 and non-RT1-incompatible). Cyclosporin A-treated and untreated recipient animals (Lewis) received allovital and antibiotic-treated viable allografts implanted into the infrarenal aorta. Second-set skin grafting was performed 3 weeks after heterotopic valve implantation to test for immunogenicity and presensitization. The animals (Lewis) were sacrificed serially on days 20, 50, 100, and 150 for immunofluorescence study using mouse monoclonal antibodies (OX6) directed at class II endothelial surface antigens. The allografts in weakly allogenic strains showed no humoral response under a short course of cyclosporin A. The cyclosporin A-untreated allovital grafts and the viable (antibiotic-treated) valves demonstrated fibrocalcification on the 100th and 150th postoperative days, respectively. In conclusion, it seems that a short course of nontoxic immunosuppression could arrest allograft rejection and thus prevent early degeneration of allografts. Furthermore, antibiotic-treated viable allografts seemed to be more durable than allovital grafts.