Dopamine-beta- hydroxylase is an enzyme that is localized to catecholamine-containing vesicles in sympathetic nerves and the adrenal medulla, and is also found in the serum. Treatment of rats with 6-hydroxydopamine, a drug which destroys sympathetic nerve terminals, leads to a decrease in serum dopamine-beta-hydroxylase activity. The decrease is not due to an effect on the adrenal medulla or to an increase in circulating inhibitor or inhibitors of enzyme. These data represent evidence that at least a portion of the circulating dopamine-beta-hydroxylase activity arises from sympathetic nerve terminals.