Anterior pituitary (AP) GABA receptors have been shown to play a functional role in the inhibitory control of prolactin (PRL) secretion by this amino acid. However, the physiological significance and the pharmacological characteristics of these receptors have yet to be determined. In normal male rat AP's incubated in vitro, GABA (10(-6) M) is effective in decreasing PRL release only when incubated in the presence of ethanolamine-O-sulphate (EOS), a potent GABA-transaminase (GABA-T) blocker. The failure of GABA alone to inhibit PRL release in vitro could be explained by the rapid degradation of the amino acid when added to the medium by AP-GABA-T. Central nervous system (CNS)- and AP-GABA receptors present similar affinity constants when evaluated by Scatchard analysis. However, displacement studies show that AP-GABA receptors have 10- and 100-times less affinity for muscimol (M), a GABA agonist, and for bicuculline, a GABA antagonist, respectively, than have GABA receptors. The low affinity of the agonist towards the AP receptors could also account for the relatively poor sensitivity of lactotrophs to GABA-mimetic compounds. Failure of chronic treatment with aminooxyacetic acid, a GABA-T inhibitor, to modify the PRL-lowering effect of GABA-mimetic compounds, despite the decrease in the number of AP-GABA receptors, indicates that in normal conditions only a reduced number of receptors are operative. These studies of AP-GABA receptors provide insight for a better understanding of the mechanisms involved in the regulation of PRL secretion by the hypothalamic GABAergic system.