Gastrointestinal (GI) peptide tissue levels were measured following intestinal transplantation in rats and evaluated as a possible early marker of transplant rejection. Vascularized syngeneic and allogeneic jejunal transplants were performed in rats without immunosuppressive therapy. Serial tissue samples of transplanted intestine were obtained from each group of animals. Baseline levels of peptides were determined in nontransplanted jejunum of the same animals. Results were correlated with histology at all experimental time points. Tissue levels of gut peptides (somatostatin, vasoactive intestinal peptide and substance P) were determined by two methods--immunoperoxidase staining and radioimmunoassay. Normal levels of gut peptides in syngeneic bowel were maintained up to 1 year after transplantation. Allogeneic bowel showed a progressive decline in gut peptide concentrations simultaneously with (or preceding) histologic evidence of rejection. The monitoring of GI peptide tissue levels may prove to be a useful method of detecting small bowel transplant rejection.