Both respiratory and metabolic acidemia stimulate the secretion of adrenocorticotropic hormone (ACTH), vasopressin, and renin. The present study was designed to test the blood pressure, heart rate, and endocrine responses of conscious sheep to low-rate infusions of H+. We infused HCl and lactic acid at a rate of 500 mueq/min into the inferior vena cava of seven chronically catheterized adult sheep. Control experiments in six sheep consisted of infusion of HCl at a rate of 100 mueq/min. Only the 500 mueq/min infusion of HCl stimulated reflex responses. This infusion increased mean arterial blood pressure and plasma ACTH concentration but transiently decreased blood pH only after the onset of the reflex responses. Heart rate appeared to increase initially but then decreased. Overall, the apparent changes in heart rate were not statistically significant. None of the infusions significantly altered plasma renin activity or vasopressin concentration. We speculate that heart rate, plasma renin activity, and vasopressin may have been partially inhibited by the increase in blood pressure. However, the lack of effect of lactic acid suggests that the HCl stimulated reflex ACTH and blood pressure responses via a mechanism not related to the concentration of the acid in the infusate or to the total amount of acid infused. It is possible that HCl, but not lactic acid, stimulated release of a humoral agent that stimulated ACTH secretion directly or reflexly. The results do not appear consistent with the stimulation of a venous chemoreceptor sensitive to H+.