The role of dopamine autoreceptors on nerve terminals in controlling the activity of tyrosine hydroxylase in the striatum was examined using a model involving supramaximal electrical stimulation of the nigro-neostriatal fibers and accumulation of 3,4-dihydroxyphenylalanine (DOPA) as a measure of the activity of tyrosine hydroxylase in vivo. In this way effects of drugs on impulse flow in these neurons could be negated and the effects on dopamine autoreceptors evaluated. Electrical stimulation, haloperidol, pimozide and clozapine increased the activity of tyrosine hydroxylase in vivo while trivastal, a dopamine agonist, had no significant effect. Combination of electrical stimulation with haloperidol or pimozide produced an additive effect on the activity of tyrosine hydroxylase, consistent with blockade of autoreceptors on nerve terminals. The combination of stimulation with clozapine (a drug shown to have minimal blocking action on autoreceptors in this model) produced an effect equivalent to stimulation alone, consistent with a lack of effect on autoreceptors. Trivastal reduced the effect of electrical stimulation, indicating a stimulatory action on dopamine autoreceptors on nerve terminals. These data are consistent with the theory of regulation of the activity of tyrosine hydroxylase in dopaminergic nerve terminals of the striatum by means of dopamine autoreceptors.