In patients with enteric drainage of pancreas transplants, urinary amylase cannot be used as a marker of rejection. Since most of the patients in our center have enteric drainage, the aim of this study was to evaluate serum lipase as a potential marker for rejection. From July 1994 to March 1997, 100 patients underwent pancreas transplantation with enteric (78) or bladder (22) drainage. Forty-two of the 100 patients had both daily serum lipase (sLip) values and either kidney core or fine needle aspiration biopsies of the pancreas and/or kidney. Thirty-one of the 42 had biopsy proven rejection and were treated on day 0 (D0). From day - 7 (D - 7) to day + 7 (D + 7), slip, serum amylase (sAmy), fasting blood sugar (FBS) and serum creatinine (sCr) were measured daily. Serum lipase values rose from 322 +/- 107 IU/L on D - 2 to 634 +/- 247 IU/L on D - 1 (p = 0.0203) in 22 of the 31 patients with biopsy proven rejection (sensitivity 71%). The rise in sCr in combined kidney pancreas transplants with biopsy proven rejection was a better marker than slip (sensitivity 86%). The sensitivity of sAmy and FBS was 50 and 33%, respectively. Other than sCr, slip appeared to be the best marker for acute rejection in enterically drained pancreas transplants which should be useful as a non-invasive indicator of rejection in solitary pancreas transplants where sCr cannot be used.