It has long been recognized that hypotheses relating the affective disorders to alterations in biogenic amine metabolism were, at best, reductionistic oversimplifications of very complex biological states that undoubtedly involved many other biochemical, physiological, and psychological factors. The body of research summarized in this review, however, attests to the heuristic value of these reductionistic hypotheses, initially formulated on the basis of the neuropharmacological effects of drugs used in the treatment of the affective disorders. (71 pp.)