245 Short term results with tacrolimus (tac) therapy for refractory acute renal allograft rejection (RARAR) are well documented, however, additional data is needed regarding long-term outcomes. We present the results of a four year experience with an aggressive approach toward tac therapy for RARAR.Methods: RARAR was defined as biopsy-proven acute rejection occurring after a course of OKT3 or polyclonal antilymphocyte antibody therapy. Exclusion criteria consisted only of chronic rejection, defined as baseline serum creatinine (SeCr) > 3.0 mg/dl with biopsy showing chronic rejection. Tac therapy was initiated at 0.3 mg/kg/day and adjusted to provide initial target levels of 15-25 ng/ml. Renal allograft biopsies were performed weekly until rejection reversal was documented. Results: A total of 48 patients have been treated for RARAR since August 1993. Demographic data includes: Age 42.6 ± 13.7 yr; 22 females, 26 males, 32 blacks, 13 Caucasians, 2 Hispanics, and 1 Asian. Immunologic risk factors include: 43 primary transplant recipients, 5 secondary; HLA matching; A/B loci 0.95 ± 1.21 Ag/pt, DR loci 0.58 ± 0.66 Ag/pt; PRA peak 17± 23%, current 11 ± 22%. Mean and median followup were: 33± 15 and 35 months. Median time to first rejection, antilymphocyte Ab therapy, and tacrolimus rescue therapy were 28, 33, and 91 days. Pre-tacrolimus antirejection therapy consisted of 46 ± 31 mg/kg prednisone equivalent dose, and 12 ± 5 days of antilymphocyte Ab therapy. Actuarial graft and patient survival at 6, 12, 24, and 36 mo were; graft = 87, 82, 74, 70% and patient = 96, 95, 94, 94%. SeCr values included: pre 2.7 ± 1.0, 1 yr 2.0 ± 0.9, 2 yr 2.0 ± 0.7, 3 yr 1.5± 1.0 mg/dl. Twenty-two recurrent rejection episodes were diagnosed in 16 patients (33%), and were successfully treated without antilymphocyte preparations. Tac dosing (mg/kg/day) included: Day 7 = 0.28 ± 0.06, 6 mo = 0.17 ± 0.12, 1 yr = 0.14 ± 0.11, 2 yr = 0.12 ± 0.07, 3 yr = 0.1 ± 0.1. Tac trough levels (ng/ml) included: Day 7 = 18.7± 12.9, 6 mo = 9.1 ± 6.5, 1 yr = 8.2 ± 4, 2 yr = 6.0± 2.0, 3 yr = 5.2 ± 0.2. Prednisone dosing (mg/kg/day pred equivalent) included: Day 1 = 0.3 ± 0.13, 6 mo= 0.17 ± 0.07, 1 yr = 0.07 ± 0.05, 2 yr = 0.05 ± 0.08. Opportunistic infections did not occur after 1 year, and PTLD was not observed. Conclusions: Tacrolimus therapy for RARAR: 1) provides good long-term patient and graft survival, 2) allows for good preservation of renal function, and 3) lower dosing of tacrolimus and prednisone may be achieved with good long-term results.