Drugs of abuse interfere with the adrenergic activity at the periphery and the study of their effects In Vivo at this level may contribute to understand the central mechanisms of action. Free and sulfoconjugated catecholamines and serotonin (5-hydroxytryptamine, 5-HT) were measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD); plasma dopamine (DA)-b-hydroxylase (DBH) activity was determined by a HPLC technique. When compared with healthy subjects (n = 49), the results in drug addicts (n = 48) revealed: a) Significant increases in plasma DA (free and sulfoconjugated), epinephrine (Epi)- and norepinephrine (NE)-sulfate levels; b) no significant differences in the levels of plasma free NE or Epi, serum and platelet 5-HT. Concerning DBH activity, there was a tendency for an increase. In conclusion, since catecholamines are rapidly inactivated during blood circulation, the measurement of their sulfates may better reflect catecholamine turnover. The differences found may be interpreted as a reflection of the activation of adrenergic neurotransmission, principally as a consequence of catecholamine uptake blockade by cocaine. Finally, in our conditions the abuse of cocaine plus heroin does not significantly interfere with 5-HT uptake by platelets.