Anterior pituitary glands from chickens (Gallus domesticus) were incubated with or without single, mediobasal chicken hypothalami in medium containing histamine, alone or together with the antagonist diphenhydramine or in medium containing gamma-aminobutyric acid (GABA), alone or together with the antagonists bicuculline or picrotoxin. The release of prolactin (Prl) and growth hormone (GH) was measured by homologous radioimmunoassay. Histamine had no direct effect on the release of either hormone but stimulated Prl (in a dose-related way) and GH release when anterior pituitary glands were co-incubated with hypothalami. Diphenhydramine also had no direct effect on Prl or GH secretion but blocked the stimulatory effect of histamine on hypothalamus-induced Prl and GH release. When anterior pituitary glands were incubated without hypothalami, GABA, bicuculline and picrotoxin had no effect on the release of Prl or GH. However, GABA inhibited the release of both hormones in a concentration-related manner, when anterior pituitary glands were co-incubated with hypothalami. This inhibition was blocked by both bicuculline and picrotoxin. These results suggest that histamine and GABA may be involved in controlling the secretion of Prl and GH from the avian pituitary gland, possible by modifying the secretion of hypothalamic releasing and/or release-inhibiting hormones.