The relevance of local removal and release of norepinephrine (NE) for antecubital venous plasma NE concentration was studied in 22 healthy subjects. Arterial and venous plasma NE and forearm blood flow were measured during intra-arterial infusion of two doses of NE, intra-arterial NE infusion with two doses of sodium nitroprusside, intravenous infusion of NE with intra-arterial infusion of four doses of sodium nitroprusside, and lower body negative pressure of -20 mm Hg for 15 minutes. The venous plasma NE concentration-time curves during the infusions of the two doses of NE indicated first-order kinetics for forearm extraction: forearm NE extraction rate during the low dose infusion was 67 +/- 4.1% (SEM) and correlated with basal forearm blood flow (r = -0.64, p less than 0.03, n = 12). Local sodium nitroprusside-induced vasodilatation during the intra-arterial and intravenous NE infusions was accompanied by dose-dependent decreases in forearm extraction rates for NE and epinephrine. During lower body negative pressure, taking into account the high basal forearm extraction rate for NE, local and systemic release of NE was indicated by increases in arterial and venous plasma and the venous-arterial plasma NE concentration difference (p less than 0.05 for all). These data show that removal of NE from forearm circulation is a process with a high extraction ratio obeying first-order kinetics and that this extraction process inversely relates to forearm blood flow. Thus, antecubital venous plasma NE is likely to be derived mainly from local release and not from the arterial plasma NE input.