Exercise and the endogenous opioids have been linked to anorexia nervosa. This investigation determined the effects of the weight-loss syndrome induced by voluntary exercise (22.5 h/day) in food-restricted rats (1.5 h/day food access) on the endogenous opioids. The animals were tested under resting-fed and 2-deoxy-D-glucose (2DG) stimulated conditions. Weight-matched, freely fed exercised and ad libitum fed unexercised groups served as controls. Specific opioid abnormalities were found in the syndrome. These included a basal elevation in plasma beta-endorphin, which was abnormally suppressed by 2DG, and 2DG-induced elevations in arcuate hypothalamic beta-endorphin content and supraoptic hypothalamic dynorphin-A content. None of these changes occurred in controls. Finally, it was found that short-term moderate exercise itself chronically reduced adenohypophysial beta-endorphin content and elevated supraoptic dynorphin-A content. The relationship of the syndrome's hyperendorphinism to the hypothalamo-pituitary-adrenal axis and the auto-addiction hypothesis of anorexia nervosa was considered, as was the significance of the supraoptic dynorphin-A abnormality to the hypothalamo-neurohypophysial system. The differential sensitivity of the supraoptic dynorphin-A system compared to the arcuate hypothalamic beta-endorphin system to moderate exercise was also discussed.