INTRODUCTION: Sodium intake has profound effects on systemic and renal sympathetic activity, but its effects on sympathetic activity in skeletal muscle vascular beds, a site at which local regulatory mechanisms could alter vascular tone directly, are unclear. METHODS: To determine the effect of dietary sodium intake on basal and isoproterenol-stimulated systemic and forearm norepinephrine kinetics, we studied seven healthy male volunteers twice, 4 weeks apart, while they were receiving a low-sodium (10 mmol sodium/24 hours) diet and a high-sodium diet (250 mmol sodium/24 hours). Forearm blood flow, measured by plethysmography, and systemic and forearm norepinephrine spillover, measured by radioisotope dilution, were determined before and after intra-arterial infusion of 60 and 400 ng/min isoproterenol. RESULTS: Baseline (before isoproterenol) systemic norepinephrine spillover was higher when subjects received the low-sodium diet (448.1 +/- 55.7 ng/min) compared with the high-sodium diet (269.7 +/- 42.7 ng/min; p < 0.05). In contrast, sodium intake did not affect local forearm norepinephrine spillover, either at baseline (low-sodium diet, 2.05 +/- 0.48 ng/min versus high-sodium diet, 2.63 +/- 0.79 ng/min; p = 0.50) or after stimulation with isoproterenol in doses of 60 ng/min (low-sodium diet, 8.84 +/- 2.2 ng/min versus high-sodium diet, 6.1 +/- 1.9 ng/min; p = 0.38) or 400 ng/min (low-sodium diet, 16.4 +/- 4.5 ng/min versus high-sodium diet, 16.7 +/- 2.5 ng/min; p = 0.93). CONCLUSIONS: Under conditions of low sodium intake, systemic norepinephrine spillover was increased but forearm norepinephrine spillover was not, suggesting that alteration in sodium intake may produce a differential effect on norepinephrine spillover in different tissues but that decreased local sympathetic activity in skeletal muscle is not the likely mechanism by which a low-sodium diet may lower blood pressure or attenuate stress-induced pressor responses.