The effect of halothane on the release and metabolism of norepinephrine during resting conditions and in response to electrical stimulation at 2 Hz was studied in isolated superfused segments of dog saphenous vein. Liquid chromatography with electrochemical detection was used to measure endogenous norepinephrine overflowing in response to electrical stimulation and the content of norepinephrine remaining in the tissue after stimulation. In other preparations, norepinephrine stores were labeled with [3H]norepinephrine, and measurements were made of [3H]norepinephrine and its metabolites (separated by column chromatography) in superfusates. Radiolabeled metabolites of norepinephrine produced intraneuronally (3,4-dihydroxyphenylglycol) and extraneuronally (O-methylated) were quantitated by liquid scintillation spectrometry. Electrically stimulated release and overflow of endogenous norepinephrine was decreased 11.9% at 0.75% halothane, 17.7% at 1.5% and 19.2% at 2.5% halothane. At each halothane concentration studied, the per cent of tissue NE content released in response to electrical stimulation was less. Halothane decreased the fraction of radioactivity lost during basal conditions and during stimulation. Less oxidative deamination of norepinephrine occurred in the presence of halothane.