Intraventricular injection (3V) of GABA can lead to a dose-related increase in plasma LH in ovariectomized (OVX) and OVX, estrogen-primed animals. Since the effects were blocked by the GABA receptor antagonist, bicucculine (B), they appear to be specific. These alterations in plasma LH were accompanied by alterations in hypothalamic LHRH, dopamine (DA) and norepinephrine (NE) content which suggests roles for all three compounds in the genesis of the increase in plasma LH. Since the DA receptor blocker pimozide (P) failed to block the elevation in LH induced by GABA it appears that the effect of GABA on LH release is mediated by NE. Others have found that the GABA agonist, muscimol, can lower plasma LH under certain conditions. Consequently, it appears likely that there may be opposite actions of GABA on LHRH release depending on the site of action within the hypothalamus. Intravenous (iv) injection of B in OVX rats produced an initial fall in plasma LH followed by a prolonged rise which again suggests several sites of action of GABA on LH release. GABA had no effect on FSH release consistent with separate control of this hormone. 3V injection of various doses of GABA produced a dose-related lowering of plasma TSH in OVX rats which appeared to be mediated by the dopaminergic system since P abolished the TSH-lowering of GABA. Following iv injection of B in normal male rats, there was a dramatic decline in TSH suggesting that under these conditions GABA would have a stimulatory action. Similar results were seen in OVX rats. The results indicate an important stimulatory action of GABA on TSH release in both males and OVX females. Perhaps the discrepancy between the results with B and GABA can be explained again by multiple sites of action of GABA of opposite sign. 3V injection of GABA induced a dose-related stimulation of growth hormone (GH) secretion; however, more recent evidence from other laboratories suggests that under certain conditions GABA has an inhibitory role in GH secretion. Again, we speculate that GABA had dual sites of action of opposite sign to affect GH. In contrast to the effects of GABA on these pituitary hormones, it appears to have a direct inhibitory effect on prolactin (Prl) secretion via the lactotrophs. Both stimulatory and inhibitory actions of GABA have been found following its injection into the brain. Studies with iv B also support dual actions on Prl release.