This study was done to investigate the possible role of histaminergic systems in electroshock seizures. Brain histamine concentrations in rats were elevated by metoprine (i.p.), an inhibitor of histamine-N-methyltransferase. Animals were tested for their response to maximal electroshock (MES) at different times after the injection. Metoprine raised brain histamine concentrations and inhibited maximal hindleg extension after MES in a dose-dependent manner. Sensitivity to seizures correlated inversely with histamine concentrations. These results suggest that histaminergic neurones are involved in mechanisms which inhibit generalizations of epileptic discharges in the brain.