The effect of dopamine (DA)-mimetic drugs on the turnover rate of gamma-aminobutyric acid (GABA) in the superficial and deep layers of superior colliculus (SC) was studied. As an index of GABA turnover, the rate of accumulation of GABA was measured after irreversible inhibition of GABA-transaminase by gamma-vinyl-GABA, microinjected directly into SC. The rate of GABA accumulation in the deep layers of SC decreased by 30 to 45% after systemic administration of apomorphine, amphetamine and cocaine. This effect of DA agonists was prevented by pretreatment with haloperidol. A similar decrease in the rate of GABA accumulation in the deep layers of SC was observed after microinjection of the GABA agonist, muscimol (0.4 nmol) directly into the substantia nigra. Nigral microinjection of the GABA antagonist bicuculline (1.0 nmol), which per se did not affect GABA accumulation in SC, antagonized the effect of apomorphine on GABA accumulation in the deep layers of SC. The results indicate that the nigrotectal GABAergic pathway which terminates in the deep layers of SC is subject to regulation by DA transmission. Furthermore, the effect of DA agonists on tectal GABA turnover is mediated via GABA release in SN. In the superficial layers of SC a small but significant decrease in GABA turnover was observed after apomorphine. In contrast to the effects observed in the deep layers of SC, this effect was not dependent on GABAergic transmission in substantia nigra, but was dependent upon the integrity of visual pathways.