Conscious sheep exposed to 4 days of eucapnic hypoxia (arterial PO2 40 Torr, arterial PCO2 33 Torr) respond with sustained increases in heart rate, cardiac output, and coronary, cerebral, and respiratory muscle blood flows (Respir. Physiol. 59: 197-211, 1985). In the present investigation, seven adult ewes were studied during similar levels of hypoxia (arterial PO2 40 Torr, 4 days) after chronic section of the carotid sinus and aortic depressor nerves to determine the contribution of the arterial chemoreceptors to these responses. Ventilation and arterial PCO2 did not change, indicating that ventilatory acclimation did not occur. O2 consumption decreased by 24%. Cardiac output (thermodilution) increased by 12% for only 24 h, heart rate increased by 44-69% above normoxic levels for only 72 h, and stroke volume was unchanged. Systemic arterial pressure was unchanged, whereas pulmonary arterial pressure rose by 56%. Coronary flow (radio-labeled microspheres) increased from 155 +/- 50.4 (SE) to 299 +/- 81 ml X min-1 X 100 g-1 at 24 h and then declined to normoxic levels by 96 h. Cerebral flow rose from 62 +/- 6.5 to between 85 +/- 14.4 and 124 +/- 43.5 ml X min-1 X 100 g-1 for 96 h. These results indicate that the arterial chemoreflexes or reflexes secondary to increased ventilation are responsible for the continued elevation of heart rate, cardiac output, and coronary flow during eucapnic hypoxia.