Adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), and renin responses to hemorrhage are highly correlated to the hemorrhage-induced decreases in arterial pH. The present study was designed to test the responses of these three systems to acute fetal acidemia, produced by intravenous infusion of H+. HCl was infused into chronically catheterized fetal sheep at rates of 0.02 (n = 5), 0.10 (n = 6), and 0.50 (n = 5) meq/min. Infusions at rates of 0.10 and 0.50 meq/min significantly decreased fetal arterial pH and increased arterial PCO2. Fetal heart rate and plasma concentrations of ACTH, cortisol, and AVP were significantly increased during infusion of HCl at 0.5 meq/min. Neither fetal plasma renin activity nor fetal arterial blood pressure was significantly altered by any of the infusions. The results of these experiments suggest that fetal ACTH, AVP, and heart rate are stimulated by decreases in arterial pH and/or increases in arterial PCO2. We speculate that these responses are chemoreceptor mediated, although we cannot distinguish the apparent relative roles of peripheral and central chemoreceptors on the basis of the present study.