The effects of GABAa receptor activation on the secretion of α-melanocyte-stimulating hormone (α-MSH) from the superfused pars intermedia of the amphibian Xenopus laevis wereexamined. The GABAa receptor agonist isoguvacine inhibited secretion of α-MSH from the pars intermedia, an action completely antagonized by the chloride channel blocker picrotoxin. Isoguvacine stimulated secretion from picrotoxin-treated tissue. Both effects were blocked by the GABAA receptor antagonist bicuculline, indicating that it is a specific action via the GABAA receptor. We conclude that, besides the inhibitory chloride channel, there is a stimulatory signaling property associated with the GABAA receptor. Isoguvacine stimulated the production of c-AMP, an action that was not blocked by picrotoxin. This suggests that the stimulatory mechanism of the GABAA receptor involves, directly or indirectly, the generation of c-AMP.