532 In many transplant programs tacrolimus (FK506) has replaced cyclosporine(CSA) for maintenance immunosuppression following kidney-pancreas transplantation. We reviewed all episodes of post-transplant acute renal dysfunction (ARD) in 89 combined kidney-pancreas transplant recipients from 1988-1996 to compare therapics. ARD was defined as a >20% increase in serum creatinine level from baseline. Demographics, transplant characteristics, diagnosis, management and outcome were assessed for each episode. There were 431 episodes ARD (4.8/patient); only 3% of patients had no ARD, 35% had 1-3 events, 44% had 4-7 events, and 18% had 8-12 events during an average follow-up of 1005 days. The median time post-transplant to ARD occurrence was 146 days (mean 521 days). There were no correlations with donor and recipient age, gender, and race when comparing patients with and without ARD. However, there were significantly more episodes of ARD in the 62 CSA patients compared to the 39 FK506 patients (4.7 vs. 3.2 events/patient, p<0.005); 12 patients received both therapies. There were no differences in either baseline serum creatinine (1.6 vs. 1.6 mg/dl), percent rise in serum creatinine (41% vs. 44%), and ARD creatinine (2.2 vs. 2.3 mg/dl) when comparing CSA and FK506 patients, respectively. There were 154 biopsies performed: the most common diagnoses were acute cellular rejection, CSA toxicity, and FK506 toxicity. 120 biopsies were in patients receiving CSA; the most common diagnoses were acute cellular rejection (49%) and CSA toxicity (23%). 34 biopsies were performed in FK506 patients with the most common diagnoses being FK506 toxicity (35%) and acute cellular rejection (29%). No differences in hospital admissions were observed when comparing CSA and FK506 patients (75% vs. 71%). In conclusion, FK506 use in kidney-pancreas transplant patients is associated with less ARD; the main cause of ARD in CSA-treated patients was acute cellular rejection while in FK506-treated patients ARD was most commonly related to nephrotoxicity.