The effects of l-tryptophan (50–800 mg/kg i.p.) on motor activity in mice were studied. l-tryptophan, 800 mg/kg, caused a reduction of motor activity while lower doses had no significant effect. The role of different metabolites of l-tryptophan in behavioural depression was tested by pretreating groups of animals with inhibitors of tryptophan hydroxylase (p-chlorophenylalanine), peripheral aromatic amino acid decarboxylase (DC) (MK-486), peripheral and central DC (NSD 1015), or tryptophan pyrrolase (allopurinol). None of these pretreatments antagonized the l-tryptophan induced depression of motor activity. Pretreatment with MK-486 or NSD-1015 potentiated the depression. Pretreatment with allopurinol potentiated as well as prolonged the depressive effect. Pretreatment with chlorimipramine had no significant effect on the l-tryptophan induced depression. The elevations of brain tryptophan and 5-hydroxytryptamine (5-HT) concentrations after l-tryptophan (800 mg/kg i.p.) were prolonged by pretreatment with allopurinol. The l-tryptophan induced increases in brain concentrations of 5-HT and 5-hydroxyindoleacetic acid were more pronounced after pretreatment with allopurinol. It is suggested that the l-tryptophan induced reduction of motor activity in mice is mediated via the amino acid itself and not via its metabolites.