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Metabolic rate and energy consumption increase through the activation of the hypothalamic-pituitary-adrenal axis when an animal is exposed to a stressor. Residual feed intake (RFI) as a measure of efficiency has been shown to be related to exogenous adrenocorticotropin hormone (ACTH)-stimulated cortisol concentrations, which is indicative of the relationship between an animal's response to stress and the efficiency with which the energy is used for growth and production. In this study, we tested the hypothesis that sheep with low post-ACTH serum cortisol concentration relative to the other sheep in the flock have lower RFI values and lower cortisol concentrations following insulin-induced hypoglycemia. Adrenocorticotropin hormone (2.0 microg/kg body weight)-stimulated cortisol concentrations were measured in 100 sheep. The extreme responders were selected (n = 12 high cortisol, n = 12 low cortisol), and feed efficiency and body composition parameters were measured. A second ACTH challenge and an insulin challenge were administered. More efficient sheep (more negative RFI value) were found to have lower (P < 0.05) cortisol concentrations following both an ACTH challenge and an insulin challenge. Low-cortisol sheep (low response to ACTH or insulin) were found to have a lower (P < 0.05) proportion of fat tissue in comparison to the high-cortisol animals. These data clearly indicate that an animal's response to exogenous ACTH or insulin-induced hypoglycemia as a stressor is related (P < 0.05) to efficiency of energy use when measured as RFI. These data have important implications in enabling identification of animals that are superior in terms of feed efficiency and for understanding the physiological mechanisms underlying efficiency of energy use.