Over the past 4 years considerable data has indicated that insulin increases skeletal muscle blood flow in healthy humans and insulin- resistance in NIDDM and obese skeletal muscle is accompanied by a diminished vascular response. It is not known whether the increase in muscle blood flow is due to enhanced flow to previously perfused muscle or to recruitment of new capillary beds. Using two techniques developed in our laboratories, we will test the hypothesis that insulin and IGF-I act to open new capillary beds. Recent studies with this protocol have now demonstrated an effect of physiologic doses of insulin to increase muscle capillary perfusion volume in normal human skeletal muscle. These are the first studies that have provided measurements of capillary blood volume in human muscle. An abstract describing these results has been submitted to the June meeting of the American Diabetes Association. Current studies are focusing now on comparing the effects of insulin in healthy, lean individuals, healthy obese individuals, and obese individuals with Type II diabetes.