To examine the disposition of [3H]norepinephrine ([3H]NE) in adrenergically innervated veins, helical strips of canine saphenous veins were incubated in Krebs-Ringer solution containing D,L[3H]NE (2 X 10(-7) M) for 2 h. [3H]NE and its metabolites were measured in extracts of veins and in superfusate (Krebs-Ringer) collected during basal conditions and during release of [3H]NE evoked by electrical stimulation (1-8 Hz), tyramine (5 X 10(-6) to 5 X 10(-4) M), or high concentrations of potassium (35-100 meq/liter). During basal conditions, the efflux from veins comprised mainly metabolits of [3H]NE, especially 3,4-dihydroxphenylglycol (DOPEG) and 3-methoxy-4-hydroxyphenylglycol (MOPEG); this pattern was unchanged by cocaine treatment, and monoamine oxidase inhibition reduced the formation of DOPEG. During evoked release of NE, the major metabolites in the perfusate were DOPEG, MOPEG, and normetanephrine, and their proportions differed with the stimulus used: O-methylated metabolites in the perfusate always increased more than did the deaminated catechol compounds; DOPEG and MOPEG were released in greater amounts than the corresponding acids; and cocaine treatment caused a higher content of all metabolites except DOPEG. 3-Methoxy-4-hydroxymandelic acid was also formed by the vein but was retained in the tissue.