Plasma corticosterone levels were used to assess the response to stress induced by intraperitoneal injections of hypertonic saline in rats with lateral hypothalamic (LH) or sham lesions. Rats with LH lesions displayed a corticosterone response equal to that of normal animals under basal conditions, after control injections of isotonic saline, and 20 min after injection of hypertonic saline (1.5 M, 1.0 ml/100 g of body weight). The corticosterone response of animals with LH lesions, however, was significantly less than that of normal animals 90 min after injection of hypertonic saline when no water was available. With access to water, normal animals displayed substantial drinking (14.5 ml/90 min), which resulted in a reduction in plasma corticosterone concentrations to a level observed after a control injection of isotonic saline, but the little water ingested by animals with LH lesions (2.5 ml) had no effect on the pituitary-adrenal system. It is concluded that the failure of animals with LH lesions to drink following a hydrational challenge is not the result of an exaggerated response to stress.