We evaluated the efficiency of the acetaminophen (AC) absorption test as a marker of graft rejection in orthotopic small bowel transplantation (SBTX) in rats. Brown Norway (BN) rats were used as donors and Lewis (LEW) rats as recipients. Orthotopic allogenic SBTX was accomplished using a cuff technique for vessel anastomosis. Animals were divided into: group A (n = 9), untreated; group B (n = 15), extended small bowel resection; group C (n = 12), syngeneic SBTX without immunosuppressants; group D (n = 15), allogenic SBTX with tacrolimus (0.1 mg/kg per day); group E (n = 15), allogenic SBTX with tacrolimus (0.5mg/kg per day). Serum AC was measured 15 min following the instillation of 0.15 g/kg AC into the stomach on postoperative days (POD) 1, 3, and 7. Grafts were examined histologically. The group D grafts showed progressive acute rejection histologically, from normal on POD 1, to moderate on POD 3, and severe on POD 7. Serum AC in group D decreased significantly from 53.1 +/- 3.9 microg/ml on POD 1, to 35.0 +/- 12.0 microg/ml on POD 3, and 10.9 +/- 5.6 microg/ml on POD 7. No remarkable change was observed in the other groups. Serum AC correlated well with histological changes in rats subjected to SBTX, resulting in acute rejection. The AC absorption test could be useful for detection of progressive graft rejection in clinical SBTX.