The expression of the nucleotide receptors P2X(1), P2X(2), P2X(7), P2Y(1), P2Y(2) and P2Y(4), in the pancreas of the streptozotocin-induced diabetic rat was investigated using immunohistochemistry. In diabetic animals, P2X(7) receptor expression, normally located in the outer periphery of the islet, was increased and located inside the islet. Double-labelling experiments, using antibodies raised against insulin, somatostatin and glucagon, showed, for the first time, an increase in immunostaining for P2X(7) receptors on islet glucagon-containing alpha cells (which had migrated to the interior), while no P2X(7) receptors were found in beta and delta cells. P2Y(1) receptors were present in intra-islet capillaries, while P2Y(4) receptors were found on both alpha and beta cells. P2Y(1) and P2Y(2) receptor expression was also found in pancreatic duct cells and P2X(1), P2X(2), P2Y(1) and P2Y(2) receptors were identified in small blood vessels. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.