1. This study compared the effects of the antimanic drugs, lithium and valproic acid, on GABA and glutamine CSF concentration and on head-shakes during hyponatremia. 2. Hyponatremic and normonatremic rats were treated with 2 mEq/kg lithium and 360 mg/kg valproic acid. Behavioral observation was conducted for 120 min after which blood and CSF collection were performed under anesthesia. 3. Peritoneal dialysis with glucose induced moderate hyponatremia and doubled glutamine CSF concentrations. Both lithium and valproic acid significantly increased GABA CSF levels in normonatremic and hyponatremic animals. Valproic acid induced head-shakes and increased CSF glutamine concentration. 4. The results suggest that both antimanic drugs have similar effects on GABA, but lithium is preferred if the increase in glutamine concentration poses a problem, either in the presence or absence of hyponatremia.