In animals, the occurrence of a behavioural syndrome consisting of hyperactivity, stereotyped movements and increased body temperature can be induced by monoamine oxidase inhibitors (MAOIs), the serotonin (5-hydroxytryptamine; 5-HT) precursor, tryptophan, and serotonin reuptake inhibitors, alone or in combination. Most of these manifestations can be specifically blocked by pretreatment with an inhibitor of serotonin synthesis.The associated symptoms of myoclonus, diarrhoea, confusion, hypomania, agitation, hyperreflexia, shivering, incoordination, fever and diaphoresis can occur in patients treated with serotonergic agents. This constitutes the ‘serotonin syndrome’. Cases of the serotonin syndrome were reported after treatments with tryptophan, MAOIs, serotonin reuptake inhibitors and tricyclic antidepressants, alone or in combination. In some cases, the serotonin syndrome corresponds to a toxic reaction induced by a combination of serotonergic agents at high dosages. In other cases, a toxic and potentially fatal interaction can occur between MAOIs, tricyclic agents and selective serotonin reuptake inhibitors (SSRIs) given at therapeutic dosages.The serotonin syndrome also provides a heuristic model of the putative mode of action of antidepressants. Serotonin-related symptoms are the physical and objective expression of an antidepressant-induced increase in serotonin neurotransmission.