Glutamate is an amino acid neurotransmitter capable of producing widespread receptor-mediated neuronal excitation. Recently we reported that high doses of monosodium glutamate (MSG) given systemically stimulate food intake in a dose-related fashion. Since glutamate does not cross the blood-brain barrier, it seems possible that feeding was stimulated by an action of glutamate on neurons within circumventricular organs (CVOs), areas of the brain in which the blood-brain barrier is deficient. In this experiment, we tested the hypothesis that systemic MSG stimulates feeding by an action on the area postrema (AP), a CVO in the caudal hindbrain. AP-lesioned rats (APLs) and sham-operated controls (shams) were injected with saline or MSG (2 and 6 g/kg, SC, one dose per week). Food intake was measured for 3 hr immediately following the injection. Shams increased their food intake significantly in response to both doses of MSG, but APLs did not. This result suggests that systemic glutamate may stimulate feeding by an action on the AP.