The response of plasma ACTH and the secretory response of cortisol to moderate hemorrhage were determined in awake dogs in the morning (AM) and evening (PM). Whereas the magnitudes of the response of ACTH were similar in the AM and PM, the magnitude of the secretory response of cortisol was significantly greater in the AM compared to that in the PM. At both times of day, heart rate, mean arterial pressure, and secretory rates of epinephrine after hemorrhage were similar. These findings suggest that AM-PM differences in stimuli produced by moderate hemorrhage cannot explain the differences in the secretion of cortisol. Instead, AM-PM changes in adrenocortical sensitivity to endogenous ACTH after hemorrhage determine the AM-PM differences in the secretion of cortisol.