To explore the effects of the acute induction of hyperglycemia on sympathetic activity and vascular function we studied eight normal control subjects (28 +/- 3 years of age). Muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) were measured before (5.4 +/- 0.2 mmol/L) and during systemic infusion of 20% dextrose with octreotide (250 μg/h) and low dose insulin (4 mU.m - 2 .min - 1 ) with 60 min of hyperglycemia (venous plasma glucose, 12.5 +/- 0.6 mmol/L). To control for the effects of hyperosmolarity and volume infusion subjects returned for two control studies with equal volume 20% mannitol and 0.2% saline infusions instead of dextrose infusion. The increase in MSNA during hyperglycemia (178 +/- 48 units) was significantly greater than the increase during mannitol (69 +/- 46 units, p < 0.001) or during 0.2% saline (28 +/- 28 units, p < 0.001). The decreases in FVR after 60 min of hyperglycemia 20 +/- 4 units, p = 0.002 and mannitol 13 +/- 4 units, p = 0.033 were significantly greater than the decrease during saline (0.1 +/- 4 units). The changes in FVR during hyperglycemia and mannitol did not differ. Acute hyperglycemia causes sympathoexcitation and peripheral vasodilation. The vascular effect may be mediated by increased osmolar load.