Expression of major histocompatibility complex (MHC) molecules by pancreatic islets may influence the survival of pancreas or islet grafts in allogeneic recipients. This study compares the presence of MHC class II (HLA-DP, DQ, DX and DR)-positive cells in 27 pancreases and in 10 isolated islet preparations from human donors. Cells expressing MHC class II were present in all tissues examined as histiocytes located in interstitial areas in both the endocrine and nonendocrine components and as endothelial cells in the nonendocrine part. Endocrine, acinar and duct cells were MHC class II negative. In pancreases from donors under the age of 7 years the frequency of MHC class II-positive histiocytes was only one third of that in adults, and they rarely contained MHC class II-positive endothelial cells. The MHC class II-positive histiocytes were further phenotyped as macrophages positive for LCA and acid phosphatase, or dendritic cells negative for the latter markers. Dendritic cells were frequent in adult organs but rare in organs from donors under 7 years of age. In freshly isolated islet preparations from adult donors, less than 1% of the cells were MHC class II positive. These were identified as resident macrophages and dendritic cells. No MHC class II positive cells were encountered in the islet capillaries. The putative role of MHC class II-positive donor cells in allograft rejection suggests that these differences in MHC class II expression influence the immunogenicity of pancreatic and islet grafts in an age-dependent manner.