The effects of gamma-aminobutyric acid (GABA) on the secretion of insulin, glucagon, and somatostatin were studied in the isolated dog pancreas. Insulin secretion was inhibited in a dose-related fashion for 10 min or more by as little as 1 microM GABA. A prompt but small and transitory rise in somatostatin secretion, lasting only 1 min, occurred at GABA concentrations of 10 and 100 microM, levels that exert inhibitory effects on nervous tissue. Bicuculline, a GABA antagonist, inhibited insulin secretion and did not antagonize GABA-mediated insulin inhibition. The results suggest that GABA in concentrations that are known to exist in islet tissue can influence the secretion of islet hormones.