A wide variation in the performance of inbred rats measured in the evaluated plus maze test suggests a possible genetic basis for anxiety response (AR). To gain further insight into the role of genetics in AR, we have characterized AR in male outbred S-D rats. Rats were placed in the black compartment (BC) facing the wall opposite the aperture and time needed for the animal to exit BC was noted. All rats underwent 3 successive trials 1-1.5 hrs apart. Naive rats showed a wide variation in their AR in trial 1(mean = 89 +/- 19 sec, range = 5-360 sec). Sixty-eight% of the rats exhibiting low AR exited BC in < 30 sec, whereas 16% stayed in for the entire 360 sec (high AR). On successive testing, there was a progressive increase in AR which reached to max on second trial (Trial 1: 89 +/- 19, Trial 2: 171 +/- 23, Trial 3: 210 +/- 22 sec, p < 0.0001). The time spent in BC on successive trials increased for most rats (33/44), decreased for some (2/44), showed min to no change (5/44) or erratic response (4/44) for others. In conclusion wide variation in the AR in outbred rats could be exploited to study genetic and neurochemical mechanisms of anxiety.