A possible antimanic property of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind placebo-controlled ABA design in 5 acutely ill manic patients. In 4 cases a marked improvement was observed after valproate medication whereas one patient showed no response. Seven further patients with frequently recurrent episodes of a manic or maniform schizoaffective psychosis, irresponsive to lithium prophylaxis, were chronically treated with valproate in combination with low doses of lithium (one case only with valproate). Over an observation period of 1 1/2-3 years none of the patients exhibited a relapse. It is proposed that, in general, GABA-ergic anticonvulsants possess antimanic properties and that the specific antimanic effect of lithium is due to a GABA-ergic mode of action. The possible role of GABA-systems in affective disorders and in organic types of psychoses (e.g.,porphyria-psychosis, delirium tremens) is discussed on the basis of pharmacopsychiatric considerations.