The International Pancreas Transplant Registry data base was analyzed for the effect of HLA and mismatching on pancreas survival rate. Typing data was available for both donor and recipient at the A, B and DR loci in 524 of 855 cadaver cases reported since 1982 and in 37 related cases. For cadaver cases, the 1-year functional survival rates for grafts mismatched at less than or equal to 3 (N = 163) versus greater than or equal to 4 (N = 361) A, B and DR antigens were 49% versus 39% (P = 0.121); for technically successful (TS) cases the rates were 66% (N = 123) versus 54% (N = 257) (P = 0.038). An effect was seen at A, B and DR loci, but the differences were not significant when considered separately. THe analysis of TS related donor transplants showed a 1-year graft survival rate of 89% for HLA mismatched donors (N = 11) and of 80% for HLA identical donors (N = 11). The survival rate of the latter is significantly higher (P = 0.046) than that of the TS cadaver donor transplants (59% at 1 year, N = 361). The data suggest that the results of pancreas transplantation will be improved by minimizing HLA mismatches. However, a reanalysis with a more complete data base is needed before firm conclusions can be drawn.