A comparison of effects of the restrain stress, and lipopolysaccharide and interleukin-2 treatment on pituitary-adrenal system of tame and aggressive rats, was examined. It was found that plasma ACTH and corticosterone levels in response to restrain stress and lipopolysaccharide treatment were significantly decreased in the tame rats compared to aggressive ones. By contrast, the maximum corticosterone level was the same in plasma of both groups after interleukin-2 treatment, although the time patterns of the response were different. Thus the selection of wild grey rats for tame behavior results in change of the response of the pituitary-adrenal axis to the immune stimulus. It is conceivable that the interaction between pituitary-adrenal axis and immune system also changes in tame rats.