In this study the role of the DA system in the expression of defensive behavior of the mouse was investigated. C57BL/6 mice subjected to three daily defeat experiences (24 h apart) exhibited an increase of defensive behaviors (upright and sideways postures and escape) as well as a decrease of activity and a decrease of social investigation compared with undefeated mice (controls) when confronted with nonaggressive Swiss mice 24 h after the last aggressive confrontation. The selective D2 DA receptor antagonist (-)-sulpiride administered before confrontation with nonaggressive opponents (fourth day) dramatically decreased defensive behaviors and produced an increase of social investigation. The selective D1 DA receptor antagonist SCH 23390 did not affect either defence or social investigation. In further experiments the behavioral effects of the selective D1 agonist SKF 38393 and of the selective D2 agonist LY171555 on naive C57BL/6 mice interacting with nonaggressive opponents of the same strain were assessed. SKF 38393 in doses up to 30 mg/kg did not produce any significant behavioral changes while LY171555 produced a clear-cut dose-dependent increase of defensive behavior as well as a decrease of social investigation and activity and an increase of immobility. The behavioral profile produced by the D2 agonist did not differ from that produced by defeat experiences. These results indicate that D2 receptors play a major role in the expression of defensive behavior in the mouse. The hypothesis that alteration in D2 receptor functioning may produce hyperdefensiveness possibly due to altered perceptive processes is discussed.