Using cultured endothelial cells from porcine aorta, we studied the effects of glucose and insulin on the release of immunoreactive endothelin (ET), a novel vasoconstrictor. Glucose concentrations of 27.5 and 55 mM inhibited ET release by more than 50%. Insulin (0.2-20ug/ml) and insulin-like growth factor 1 (IGF-1)(1×10-10-1×10-8M) stimulated ET release in a dose dependent manner. Twenty μg/ml of insulin and 1×10-8M of IGF-1 increased the amount of released ET by approximately 40%. These results suggest that ET release from vascular endothelial cells may vary in the presence of diabetes.