The circulating levels of the major adrenal steroids, corticosterone (Cmpd. B), deoxycorticosterone (DOC), and aldosterone were compared in male and female, arteriosclerotic, breeder and non-arteriosclerotic virgin, Sprague--Dawley rats under resting conditions, i.e., quiescence, and after exposure to a mild stress, i.e., movement from one room to another just prior to autopsy. Under resting conditions, the arteriosclerotic animals had significantly greater circulating levels of Cmpd. B, DOC and aldosterone than the non-arteriosclerotic animals. Both the arteriosclerotic and non-arteriosclerotic animals were able to respond adequately to the mild stress stimulus. However, the female breeder rats which manifest the most severe aortic sclerosis, showed the greatest increase in Cmpd. B and aldosterone in response to the mild stress. Although no statistically significant differences could be found between female breeders with grossly visible aortic sclerosis of clear, minimal, moderate, or severe degree, it was apparent that adrenal steroid responsiveness becomes progressively compromised with increasing severity of arteriosclerosis, e.g., unusually high or low levels of Cmpd. B and aldosterone under both quiescent and mild stress conditions. It is suggested that there may be some connection between abnormal hypothalamic-pituitary-adrenal-gonadal function in repeatedly-bred and the pathogenesis of their naturally-occurring ateriosclerosis.