The antiepileptic effect of gamma-vinyl gamma-aminobutyric acid (GABA), an irreversible GABA-transaminase inhibitor, was investigated in an add-on, placebo-controlled, double-blind, cross-over, fixed-dose trial. Twenty-one patients suffering from difficult to control complex partial seizures participated; 18 patients completed the trial. Serum levels of concomitant antiepileptic drugs were kept constant throughout the trial. Three patients (17%) experienced a 75% reduction in seizure frequency and in 8 (44%) the seizures were reduced by at least 50%. Two patients developed a moderate and 1 patient a marked increase in seizure frequency during treatment with gamma-vinyl GABA. Except for 2 patients who had to discontinue the trial because of adverse effects of gamma-vinyl GABA, the participants were unable to discriminate between treatment regimens with regard to side effects. gamma-vinyl GABA seems to be a promising new antiepileptic drug, and the first one to present convincing evidence of a GABAergic mechanism of action.