Endothelium-dependent and endothelium-independent responses to exogenous vasoactive substances were compared in isolated, perfused mesenteric beds from control rats and in rats subjected to prolonged (15-17 weeks) streptozotocin induced diabetes. The main aim of the study was to determine whether the prolonged period of diabetes altered vascular endothelial function, and thereby modified vascular responsiveness to vasoconstrictors or vasodilators. Noradrenaline induced vasoconstriction was not significantly altered in preparations from diabetic rats compared to control. Vasodilator responses to acetylcholine (ACh) and ATP were endothelium-dependent, since they were greatly reduced or abolished after endothelium removal by perfusion with 0.1% Triton-X 100. The vasodilator action of these agents was fully preserved in the diabetic animals. Sodium nitroprusside produced a vasodilation which was endothelium-independent, this vasodilation was also preserved in the diabetic animal. We conclude that prolonged streptozotocin-induced diabetes does not reduce the ability of the mesenteric vascular endothelium to release vasodilator substances, nor does it alter the responsiveness of the bed to exogenous endothelium-independent vasodilator sodium nitroprusside or vasoconstrictor noradrenaline.