The inactivation of exogenous and neural norepinephrine (NE) by helical strips of rat tail artery was studied with a combination of the techniques of transmural stimulation and oil immersion. A steady-state contraction was elicited either by adding low concentrations of NE to the bath or by low frequency transmural stimulation. The aqueous bath solution was then replaced with mineral oil and relaxation was monitored. A prolongation of the rate of relaxation of the strip at a given concentration of exogenous NE or frequency of transmural stimulation indicates that inactivation of NE has been slowed. The major known processes for inactivation of NE were inhibited by pharmacological agents used singly or in various combinations (uptake1 by cocaine, uptake2 by corticosterone, catechol-O-methyltransferase by tropolone and monoamine oxidase by iproniazid). Cocaine was the only agent which alone caused a marked shift in the relaxation curve. A modest and equivocal effect on relaxation after inhibition of extraneuronal uptake (uptake2), or catabolism of NE (catechol-O-methyltransferase and monoamine oxidase) was only demonstrated under special circumstances (high concentrations of NE, combinations of inhibitors, or uptake1 simultaneously inhibited). Low concentrations of NE, both exogenous and neural, are preferentially inactivated in rat tail artery by neuronal uptake and storage.