The mouse defense test battery (MDTB) has been designed to examine anxiogenic-or anxiolytic-like properties of psychoactive drugs through effects on specific defensive behaviors. In the present study, the MDTB was used to evaluate the potential contribution of genetic factors to these behaviors. The data revealed pronounced differences in several defense reactions among four inbred strains (BALB/c, C57BL/6, CBA, DBA/2) and one outbred (Swiss) mouse line. Thus, when subjects were introduced into the apparatus, Swiss and C57BL/6 displayed the highest levels of horizontal and vertical activities, while BALB/ c and DBA/2 mice showed intermediate and CBA low activity rates. When subjects were chased by the rat, C57BL/6 mice used flight as the dominant defense strategy, while the defensive responses of BALB/c, C57BL/6, and DBA/2 mice consisted of flight reactions and risk assessment activities. However, when flight or escape was not possible, risk assessment became the predominant feature of the defense repertoire in the C57BL/6 mice. When defensive threat/attack behaviors were required, Swiss, BALB/c, DBA/2, and C57BL/ 6 mice showed very similar reactions in terms of the magnitude of the responses observed. CBA mice were poorly defensive in all these test situations. Finally, after the rat was removed from the test apparatus, Swiss, DBA/2, and C57BL/6 mice displayed more vertical activities than BALB/c mice. These latter, however, showed an increased level of ambulation compared to the activity recorded before the rat exposure. Together, these findings indicate that genetic factors contribute to defensive behaviors in this animal model of anxiety. The different behavioral profiles displayed by the strains used here may provide the means to obtain a better insight into the neurobehavioral mechanisms involved in anxiety-related disorders.