Tryptamine is an indolic compound that occurs naturally in the mammalian central nervous system. To test whether tryptamine-containing neurons are present in the nigrostriatal system, we investigated effects of unilateral electrolytic lesions of the substantia nigra on striatal tryptamine concentrations. Determinations were made 7 days after lesioning. Nigral lesions resulted in an ipsilateral reduction in accumulation of striatal tryptamine observed after monoamine oxidase inhibition. As tryptamine formation is dependent on the activity of the enzyme L-aromatic acid decarboxylase (L-AAD), which is present in monoamine-containing neurons, the reduction in accumulation of tryptamine after nigral lesions may be secondary to enzyme loss with the degeneration of dopamine-containing neurons. Nevertheless, failure to observe decreases in the accumulation of tryptamine after raphé lesions, which deplete striatal 5-HT and L-AAD, indicates that tryptamine may be associated specifically with neurons in the nigrostriatal system.