A variety of recent literature suggests that brain gamma-aminobutyric acid (GABA) plays an important role in the control of feeding. One such line of evidence is that pharmacological inhibition of brain GABA transaminase (GABA-T) produces dose-dependent anorexia in otherwise normal rats. To determine the generality of these findings we tested the ability of the GABA-T inhibitor ethanolamine-O-sulfate (EOS), to produce anorexia in three animal models of obesity: rats with medial hypothalamic lesions, rats exposed to palatable foods or Zucker fatty rats. Following intracisternal injection of 100, 200 or 400 micrograms EOS, all three models of chronic overeating showed dose-dependent anorexia of similar magnitude and duration to that seen in appropriate controls. These observations provide empirical support for previous suggestions that treatments which enhance brain GABA neurotransmission merit investigation for their potential use in treating excess energy consumption.