The 5-HT(3) receptor antagonist ondansetron has provided a somewhat equivocal profile in a number of animal models of anxiety. The present study assessed the effects of this compound in two ethological test batteries. The Fear/Defense Test Battery (F/DTB) and the Anxiety/Defense Test Battery (A/DTB) have been developed to investigate antipredator defensive reactions in rats. The F/DTB measures behavioural reactions of wild- trapped rats to human threat, while the A/DTB assesses behavioural responding in laboratory rats as a consequence of exposure to a domestic cat, and to cat odour per se. Ondansetron (0.001-0.10 mg/kg) failed to provide any reliable and consistent profile of anxiety/fear reduction in either test battery. In addition to the elucidation of drug effects, previous studies have provided clear evidence of gender differences with female rats showing higher levels of defensiveness than males in the A/DTB. Until now, no such differences have been observed with wild-trapped rats in the F/DTB. Thus, the present study indicated a clear gender difference with females exhibiting greater defensiveness. This finding is discussed with reference to the general decrease in defensiveness of the first generation animals compared with their wild-trapped parents.