Three studies were done to determine whether serum dopamine-beta-hydroxylase (DBH) activity is affected by the symptoms of depression or anxiety. In the population-screening study, serum DBH activity was measured in a heterogeneous sample of 548 medical, surgical, and psychiatric outpatients. No association was found between serum DBH activity and scores on either the Zung Self-rating Depression Scale or the Taylor Manifest Anxiety Scale. In the longitudinal depression study, enzyme activity was measured in 14 patients with major depressive illness treated with imipramine. Serum DBH activity remained unchanged throughout treatment whether or not the patient recovered from the depressive illness. Furthermore, there was no association between enzyme activity and steady state antidepressant plasma levels. In the longitudinal anxiety study, evaluation of 45 anxious outpatients in a placebo-controlled double-blind evaluation of two benzodiazepines (diazepam and alprazolam) indicated that serum DBH activity failed to reflect either state changes in anxiety or pharmacological variables. These results are reviewed with respect to current knowledge regarding neuronal release and extraneuronal disposal of circulating DBH.