The effect of alcohol on aggressive behavior was studied in the highly aggressive transgenic TGF alpha male mouse. In contrast to findings obtained in other aggressive animals, low and moderate doses of alcohol failed to reduce this behavior in the TGF alpha mice; only a high dose reduced aggression. The plasma levels of alcohol were similar in the TGF alpha mice and non-transgenic control mice. However, the loss of righting reflex following an alcohol administration was significantly lengthened in the TGF alpha mice. These results suggest that the male TGF alpha mice can be used to investigate the mechanisms determining the physiological sensitivity to alcohol. Furthermore, these mice represent the first animal model supporting the findings obtained in humans that alcohol maintains pathological aggression.