The serotonin hypothesis postulates a decreased function of this neurotransmitter in the central nervous system of depressed patients. L-tryptophan and--more specific--5-hydroxytryptophan are natural precursors of this biogenic amine. Results of numerous therapeutic trials with L-tryptophan are not convincing of this compound's antidepressant efficacy in marked to severe endogenous depressions. On the other hand, it cannot be excluded that it is effective in moderate dysphoric states with apathy and sleep disturbances. However, possible toxic effects of high and long term use render its clinical use doubtful. The antidepressant efficacy of 5-hydroxytryptophan has not been proven. However, the possibility exists that a serotonin deficient subgroup of depressed patients responds to this substance and further, that it has depression prophylactic properties. As both tryptophan and 5-hydroxytryptophan are less effective than tricyclic antidepressants and not without side effects they do not appear to be useful antidepressants.