In a model of fully allogeneic heterotopic rat small bowel transplantation, the changes in intraepithelial lymphocyte (IEL) number and subpopulations were analysed. During early phases of rejection (5th postoperative day) a 4-fold increase in the number of IEL was observed when compared with native small bowel (4.05 vs. 15.84IEL/100 epithelial cells). When cyclosporine was given, counts were still as high as 11.4 and 12.58 on the 5th and 10th postoperative days, respectively. The percentage of CD8+ IEL, constituting a major population (84%) in the untreated small bowel, was significantly decreased (46.4%) during early phases of rejection. At that time, the majority of intraepithelial mononuclear cells were both CD8- and CD4-. In cyclosporine-treated animals, this was not observed until the 10th postoperative day. Some 23% of IEL in untreated animals expressed MHC class I antigens of the host; 17.2% (5th postoperative day) and 19.8% (10th postoperative day) did so in the cyclosporine-treated animals. Transmission electron microscopy revealed lymphocytes that bore cytoplasmic buds and pseudopods protruding between the enterocytes. There was no morphological difference between the IEL of rejected allografts and native small bowel. Due to the unspecific histologic changes associated with rejection, interpretation of histopathologic findings in mucosa biopsies of the allograft can be rather troublesome. An increase in the number of IEL is therefore a welcome additional marker of rejection.