It was found in our earlier experiments that infusion of β-endorphin (β-End) into the 3rd brain ventricle in sheep elicited a differential effect on the secretion of cortisol under physiological and stress conditions. Under physiological conditions it elevated the level of cortisol in the peripheral blood, while in stressed animals it suppressed it. To obtain further support for the suppressive action of β-End on cortisol secretion under stress conditions a β-End antiserum was infused into the 3rd ventricle of the brain in stressed and nonstressed sheep and the concentration of plasma cortisol was measured. Stress was induced by mild electric foot shock. Infusion of the β-End antiserum during stimulation enhanced the plasma cortisol values, when compared with those obtained during the infusion of rabbit hyperimmune serum containing anti-guinea pig γ-globulins or saline. Moreover, during the infusion of β-End antiserum some aggravation of stress symptoms expressed by the increase of restlessness and higher frequency of defecations and urinations was observed. Additional experiments carried out to study the effect of β-End on prolactin (PRL) secretion showed that this opioid induced a very high secretion of PRL in stressed animals. On the basis of these data and the known suppressive action of PRL on the corticosterone response to stress in the rat, we suggest that the suppressive action of β-End on cortisol secretion in stressed sheep could be caused by the action of PRL. Conversely, blockade of β-End function by the infusion of β-End antiserum and suppression of PRL secretion could enhance secretion of cortisol and aggravate stress symptoms in stimulated sheep.