Canine isolated vein strips were labeled with 3H-norepinephrine (NE). 3H-NE and its metabolites appearing during spontaneous outflow and during electric stimulation (10 Hz, 100 V, 2 ms, 5 min) were determined. The spontaneous outflow of 3H-compounds from the vein contained 90.5% metabolic products of NE, chiefly, the O-methylated and deaminated products (OMDA) and 3,4-dihydroxyphenylglycol (DOPEG). During electric stimulation approximately a 3-fold increase in the outflow of radioactivity, consisting of 39% NE, 25% OMDA and 19% DOPEG was observed. Normetanephrine (NMN) and 3,4-dihydroxymandelic acid represented only 10 and 6%, respectively. Blockade of reuptake of NE into nerve terminals by cocaine did not prevent the appearance of deaminated metabolites in the spontaneous outflow. However, when the vein was electrically stimulated the increase of DOPEG was almost completely blocked. Blockade of extraneuronal uptake of NE by deoxycorticosterone did not significantly modify the composition of spontaneous outflow. However, deoxycorticosterone caused a marked decrease of NMN and OMDA during electric stimulation. The inhibition of catechol-O-methyltransferase by U-0521 [3,4-dihydroxy-2-methylpropiophenone] caused a decrease of NMN and OMDA during the spontaneous outflow, and a shift from O-methylation to deamination of NE. During electric stimulation, U-0521 markedly decreased the formation of NMN and OMDA and caused an increase in NE.