The increase in leg and forearm blood flow induced by insulin could be secondary to its metabolic effect on glucose uptake. We therefore investigated whether insulin causes vasodilation of the internal carotid artery, since the brain is not dependent on insulin for glucose uptake, to demonstrate that the vasodilatory effect of insulin is primary and independent of its metabolic effect. Internal carotid artery diameter was continuously monitored using a 7.5-MHz transducer linked to an Acuson XP10 ultrasonograph (Mountainview, CA) during infusion of 125 mL 10% dextrose mixed with 3 U regular insulin and 5 mmol potassium chloride over 1 hour. The internal carotid artery diameter increased progressively with time from a mean of 5.4+/-1 mm to 5.7+/-1 mm at 15 minutes, 5.9+/-1.1 mm at 30 minutes, 6+/-1.1 mm at 45 minutes, and 6.1+/-1.1 mm at 60 minutes (P < .05), an increase of 13% over baseline. Glucose was maintained between 93 and 106 mg/dL, and insulin increased from 15+/-14 microU/mL and was maintained between 34 and 47 microU/mL. There was no change in mean arterial blood pressure (MABP) or heart rate during the infusion. We conclude that insulin dilates the internal carotid artery consistently at physiological concentrations, probably independently of glucose uptake by the brain. Alterations in this effect of insulin may be of relevance in the pathogenesis of abnormalities of cerebral blood flow in type 1 and type 2 diabetics as described by our group previously.