There is accumulating evidence that insulin has a physiological role to vasodilate skeletal muscle vasculature in humans. This effect occurs in a dose-dependent fashion within a half-maximal response of approximately 40 microU/ml. This vasodilating action is impaired in states of insulin resistance such as obesity, non-insulin-dependent diabetes, and elevated blood pressure. The precise physiological role of insulin-mediated vasodilation is not known. Data indicate that the degree of skeletal muscle perfusion can be an important determinant of insulin-mediated glucose uptake. Therefore, it is possible that insulin-mediated vasodilation is an integral aspect of insulin's overall action to stimulate glucose uptake; thus defective vasodilation could potentially contribute to insulin resistance. In addition, insulin-mediated vasodilation may play a role in the regulation of vascular tone. Data are provided to indicate that the pressor response to systemic norepinephrine infusions is increased in obese insulin-resistant subjects. Moreover, the normal effect of insulin to shift the norepinephrine pressor dose-response curve to the right is impaired in these patients. Therefore, impaired insulin-mediated vasodilation could further contribute to the increased prevalence of hypertension observed in states of insulin resistance. Finally, data are presented to indicate that, via a yet unknown interaction with the endothelium, insulin is able to increase nitric oxide synthesis and release and through this mechanism vasodilate. It is interesting to speculate that states of insulin resistance might also be associated with a defect in insulin's action to modulate the nitric oxide system.(ABSTRACT TRUNCATED AT 250 WORDS)