As reported to the UNOS Kidney Transplant Registry from 1988 through 1994, 544 first cadaveric kidney graft recipients have been discharged with maintenance tacrolimus FK506 therapy. Total followup data was available on 38,057 first cadaveric kidney transplants from 224 centers reporting at least 10 grafts each to the Registry. We examined the effects of FK506 on short and longterm renal graft outcomes and compared its effect with that of cyclosporine CsA. Three drug categories FK506, CsA, and Other were defined using therapies through discharge i.e., grafts surviving more than 15 days. The 1year graft survival rate of 2366 recipients receiving Other therapies was 69.2±1.0. By comparison, both FK506 and CsA recipients demonstrated significantly improved early graft function 1yr survival rates of 91.1±1.3 and 86.6±0.2, respectively. The longterm graft survival, as measured by halflives, varied little 89 yr between Other and CsA groups, but was significantly P0.04 increased for FK506 patients to 14yrs. CsA usage was reported by all 224 transplant centers, whereas FK506 was administered at only 24 11 centers. Using multivariate methods, a drug regimen's graft survival rate was adjusted for center effects and 19 covariates. The adjusted FK506 and CsA cadaveric graft survival rates at 1 and 3 years mirrored their unadjusted rates, indicating that demographic differences did not confound our results. Based on this study, FK506 appears to be the first therapeutic agent to significantly improve longterm kidney graft survival rates.