The cells expressing MHC class II antigens play an important role in allograft rejection. We examined the expression of HLA DR antigens in human fetal pancreata ranging in gestational ages from 8 to 24 weeks. DR antigens were detected by immunohistochemical techniques using H4 and 40D MoAbs with immunoper-oxidase staining and the ABC procedure. Vascular en-dothelium was identified by goat antibodies directed to human factor VIII—related antigens. DR expression on endothelium was further confirmed by double staining of tissue sections with H4 and anti-FVIII antibodies. In pancreata younger than 18 weeks of gestation, DR antigens were found on single cells that were randomly distributed throughout the pancreatic parenchyma. These cells resembled dendritic cells in morphology, as reported previously (1, 2). Some vascular endothelial cells located in the intralobular connective tissues ex pressed DR antigens, but those in the pancreatic parenchyma were DR-negative. In 18–22 weeks, some endothelia of small vessels in the parenchyma became DR-positive. By 24 weeks, DR antigens were also expressed on medium-sized blood vessels, whereas intraislet capillaries and duct epithelia were DR-negative. The number of DR-positive cells increased rapidly from 11.2 cells/field (x400) in 12–14 week pancreata to 42.8 cells/field in 18–22 week pancreata. Most DR-positive cells in pancreata earlier than 18 weeks were dendritic-like cells, while those in older pancreata were endothelial cells. When pancreatic tissue fragments were cultured for two days in the presence of rIFN-γ, vascular endothelium and duct epithelium, both of which were other wise DR-negative, had become DR-positive. Even with this increase, DR-positive cell numbers were fewer in pancreata younger than 18 weeks of gestation as com pared with those in older pancreata. We also detected clusters of epithelial-like cells that were clearly stained for DR antigens. These cells were located in the parenchyma where insulin positive cells were generally found. Their DR-antigens had not changed during the 3-day rIFN-γ culture.