In this study we investigated the effect of insulin on striatal 5-hydroxytryptamine and tryptamine in streptozotocin-diabetic and in normal rats. Streptozotocin-diabetic rats show a reduction in rat striatal tryptophan, 5-hydroxytryptamine, and 5-hydroxyindole acetic acid, an effect observed at 7 or 14 days after the treatment began. In addition, the accumulation of striatal tryptamine in pargyline-treated rats was reduced at 14 days. Insulin administration produced an increase in rat striatal tryptophan concentration that was observed within 2 h following its administration. By 6 h, however, the striatal tryptophan concentrations were significantly reduced. No changes in rat striatal 5-hydroxytryptamine were observed following the insulin administration, but the treatment induced significant increases in 5-hydroxyindole acetic acid that were observed at 2, 3, 4, and 6 h after insulin administration. The administration of insulin to diabetic rats had a tendency to reverse the decreases in 5-hydroxytryptamine metabolism observed in these animals. Treatment with tryptophan (12–25 mg kg–1) markedly increased rat striatal tryptophan, but did not affect 5-hydroxytryptamine metabolism, an effect that was only observed after the administration of higher doses (50–100 mg kg–1). This is in contrast to the effect of insulin that produces a lesser increase in striatal tryptophan accompanied by an increase in 5-hydroxytryptamine metabolism, indicating that in addition to the inrease in tryptophan availability that it produces, it also possesses some other facilitatory effect on 5-hydroxytryptamine metabolism.