The pancreases of 14 children who died of type I diabetes were studied immunohistochemically for aberrant expression of HLA-DR antigens on islet endocrine cells. Two cases in which no residual insulin-secreting beta-cells were present had no evidence of HLA-DR expression on endocrine cells. Insulin-containing islets were present in the remainder, and HLA-DR-positive endocrine cells were demonstrable in all of them. Endocrine cells expressing HLA-DR were present in 171 of 630 insulin-containing islets from all the cases. However, HLA-DR-positive endocrine cells were not seen in 2060 insulin-deficient islets, providing evidence that of the four hormone-producing cells in the pancreas only the beta-cells expressed HLA-DR. Sections double stained for HLA-DR and the pancreatic hormones confirmed this view. Most islets in which HLA-DR-positive endocrine cells were seen had no evidence of insulitis, suggesting that within an individual islet, aberrant expression of HLA-DR on beta-cells may precede the inflammatory infiltrate.