Lewis rat recipients of long-term, surviving, orthotopic Brown-Norway rat intestinal allografts, initially treated with cyclosporin A (CyA) or FK 506, were evaluated for their functional capacity and morphology over 1 year after the immunosuppressive therapy had been discontinued. Functional parameters such as nitrogen and fat balances, maltose absorption, blood chemistry, hematologic studies, and the weight gained by the allografted animals did not differ from those of syngeneically grafted or age-matched normal animals. Immunohistochemical studies showed that the lamina propria of the allografts was repopulated with recipient MHC class II+ mononuclear cells and that a normal distribution of T helper, T suppressor/killer, and IgA+ plasma cells had occurred. However, fibrous replacement of the mesenteric lymph nodes and Peyer's patches were detected in all, and an inflammatory obliterative arteriolopathy developed in the mesenteric vasculature of half of the allografted animals. No such findings were observed in recipients of syngeneic grafts. These results demonstrate that the limited use of potent immunosuppressive agents immediately after transplantation averts rejection and is followed by recipient-type mucosal lymphocytic repopulation. Simultaneously, a clinically not recognizable chronic rejection evolves. This suggests that the timely diagnosis of chronic rejection may not be possible with the use of standard tests of gut function and random mucosal biopsies alone.