Gamma-amino butyric acid (GABA), an inhibitory neurotransmitter, has been implicated in the control of feeding behavior. This study was conducted to investigate the in vitro release of GABA in the basal medial hypothalamus (BMH) of hyperphagic lactating (L) and control nonlactating (NL) rats. Pregnant Sprague-Dawley rats (n = 10) were ad lib fed a semipurified powdered diet during the last 6 days of pregnancy until day 19 of lactation. Nonpregnant (n = 10) animals served as controls. Body weights and food intake were recorded every other day. Lactating rats demonstrated an increase in body weight as well as food intake as compared to nonlactating animals. At sacrifice, the BMH was removed and perfused (0.1 ml/min) with Kreb's Ringer buffer (KRB) ("basal" medium) using a Brandel perifusion system. KRB containing glucose (100 mM) or 2-deoxyglucose (2DG) (100 mM) was also applied to the tissue. Potassium stimulation was carried out to test for the viability of the tissues. Samples were collected every 10 min, derivatized with O-Phthalaldehyde and analyzed via HPLC. Glucose depressed, and 2DG enhanced GABA release compared to basal levels. There were no significant differences in GABA release between lactating and nonlactating groups. These data suggest that GABA release is responsive to metabolic changes in the brain.