The authors review evidence suggesting that some depressed patients have disturbances in serotonin metabolism. Research supporting the serotonin hypothesis includes: (1) cerebrospinal fluid studies; (2) postmortem examination of neurotransmitters, their metabolites, and their receptors; (3) platelet studies; (4) neuropharmacologic data; (5) neuroendocrine perturbations; and (6) reports that serotonin precursor compounds (tryptophan and 5-hydroxytryptophan) may benefit some depressed patients. The authors conclude that better designed studies are needed to test whether serotonin precursor compounds have antidepressant properties.