In our recently completed study of monoamine oxidase (MAO)-inhibiting antidepressants, clorgyline (a selective inhibitor of MAO type A in vitro) was found to maintain its selectivity in man over the 4-week clinical trial period. The production of deaminated metabolites from the MAO-A substrates norepinephrine and serotonin was markedly reduced, while no changes in the MAO-B enzyme (which was directly measured in platelets) occurred. Pargyline, in contrast, totally inhibited the MAO-B enzyme, but also inhibited MAO-A activity. Clorgyline proved to be a more effective antidepressant agent and also produced fewer side effects--suggesting that MAO-A inhibition is most closely associated with the antidepressant effects of MAO inhibitors, and that there may be therapeutic advantages to the use of selective MAO-inhibitors. Other studies of patients with affective disorders investigated (a) several approaches to predicting individual responsiveness to antidepressant agents, (b) personality features and symptoms such as anxiety and obessional thinking in depressed patient subgroups, and (c) behavioral assessment measures used in depressed and manic patients.