To determine the contribution of skeletal muscle to the insulin resistance of essential hypertension, insulin-stimulated forearm glucose uptake was quantitated in 12 control (age, 32 ± 3 years) and 12 hypertensive subjects (age, 36 ± 2 years) using the forearm perfusion technique. Peripheral insulin levels were raised acutely (∼ 60 μU/mL), while blood glucose concentration was clamped at its basal value (90 mg/dL) by a variable glucose infusion. During insulin stimulation, whole body glucose uptake was lower in hypertensive (4.5 ± .3 mg · kg⁻¹ · min⁻¹) than in normal subjects (5.8 ± .4 mg · kg⁻¹ · min⁻¹, P < .05). Similarly, the amount of glucose taken up by the forearm was markedly reduced in the hypertensive (5.3 ± .91 mg · L⁻¹ · min⁻¹) compared with the control group (8.7 ± 1.1 mg · L⁻¹ · min⁻¹). No appreciable difference was observed as to forearm blood flow (39 ± 4 mL · L⁻¹ · min⁻¹ and 37 ± 5 mL · L⁻¹ · min⁻¹) in hypertensive patients. These results indicate that skeletal muscle is a major site of insulin resistance in essential hypertension and that this defect is independent of muscle perfusion.