We have evaluated the role of GABA in the control of anterior pituitary (AP) hormone secretion by injecting it into the third ventricle of ovariectomized, ovariectomized-steroid primed and male rats. Specificity of the effects was determined by injecting the GABA blocker, bicuculline. The action of GABA directly on the pituitary was evaluated in vitro. The results indicate that intraventricular GABA can stimulate LH, growth hormone (GH) and, at high doses, prolactin (Prl) release, whereas low doses inhibit Prl and al doses inhibit TSH release. All of these actions are blocked by bicuculline. Intraventricular GABA administration is followed by an elevation of hypothalamic norepinephrine (NE) and median eminence dopamine (DA) levels and AP DA levels, which indicates that the compound stimulates both NE and DA release. The actions on GH and LH appear to proceed independently of DA, since the DA receptor blocker, pimozide, did not interfere with these effects, whereas the action to elevate Prl and to lower TSH was blocked by DA receptor blockade. Anterior pituitary hormone release by AP's incubated with GABA in vitro was unaltered except for an inhibition of Prl release by very high GABA doses, which could be blocked by bicuculline. Intravenous injection of bicuculline to assess the physiological significance of GABA in control of AP hormone secretion revealed no effect on FSH but a delayed rise in LH, an initial rise in Prl, followed by a fall, a tendency for GH values to rise and dramatic fall in TSH levels. These results suggest the possibility that GABA plays a physiological role in the control of AP hormone secretion, mainly via a hypothalamic action.