The effects of xylamine (N-2-chloroethyl-N-ethyl-2-methylbenzylamine) on tissue content and extracellular concentration of catecholamines in the rat brain were examined after systemic administration using in vivo voltammetry and high-performance liquid chromatography-electrochemical detection. Xylamine at a dose of 12.5 mg/kg i.p. reduced the extracellular concentration of norepinephrine (NE) in the cortex, while having no effect on the extracellular concentration of dopamine in the striatum. The content of NE in the cortex was reduced by approximately 41% at a dose of 12.5 mg/kg and 62% at 25 mg/kg within a 4-hr period, whereas dopamine contents remained unaltered. Both the reduction in extracellular concentration and the depleting action of xylamine on NE content were blocked by pretreatment with desmethylimipramine. The data suggest that xylamine has a selective action on the NE system that is mediated through the neuronal uptake carrier; however, the depleting action of xylamine and its effect on extracellular NE concentration may be unrelated actions.