The anxiety/defense test battery has been developed to measure defensive reactions in laboratory rats to both direct exposure to, and stimuli associated with, a natural predator, the domestic cat. The present investigation confirmed earlier findings with each test providing a distinct behavioral profile following exposure to predator stimuli. In addition, the data showed a consistent gender difference in a number of these behavioral measures, indicating that females are more defensive than males. These effects included reliability higher levels of cat avoidance and crouching, with lower levels of transits, lying and drinking for cat-exposed females. Similarly, females exposed to a cat odor stimulus showed a reliably higher level of stretch attend and flat back approach behaviors (risk assessment) towards the stimulus block. The 5-HT2 antagonist, ritanserin, failed to provide significant indication of anxiolytic activity, and had minimal influence on antipredator defensive behavior. An important exception to this profile was a reliable decrease in stretch attend behavior to a cat odor stimulus in females but not males. Overall, these findings suggest a complex relationship between gender, antipredator defensive behavior, and anxiolytic drug treatment.