Awake dogs were studied before (control) and after chronic bilateral carotid denervation (denervated) at rest and running for 3 min on a treadmill at 8 km . h-1 and at various grades, in an altitude chamber operated either at 140 m or at 4000 m for 3 h. Steady-state pulmonary ventilation (Vg) and breathing pattern (VT, fR), oxygen consumption (MO2), O2 concentrations (C) and pressures (P) in the arterial (a) and mixed venous blood (v), hematocrit (Ht) and acid-base status in arterial blood, and heart frequency (fH) were measured. From these data cardiac output (Vb) and stroke volume (Vs), ventilatory and circulatory requirements (Vg/Mo2, Vb/MO2), extraction of O2 from inspired gas (EairO2) and blood (EbO2), and capacitance coefficient of blood for oxygen (beta bO2) were calculated. Ventilatory responses to transient O2-inhalation were also studied and the aortic (AP) and pulmonary (PP) blood pressures measured in resting conditions. 1. After chronic carotid denervation the hypoxic chemoreflex drive of ventilation was reduced by about half, maximal MO2 remained unaffected at 140 m, but at 4000 m decreased 50% compared to 30% in controls. 2. In all experimental conditions, Vg/MO2, PaO2 and CaO2 were less in denervated animals than in controls, and EairO2, PaCO2 and H+ ion concentration were higher. 3. At 140 m, circulatory O2 convective transport was identical in the two groups of dogs. At 4000 m, beta bO2 increased similarly in both groups, but Vb and Vb/MO2 were higher in denervated dogs than in controls, in relation with reduced CaO2-CVO2 difference which contributed to restore PVO2 towards higher values. 4. At 140 m, mean resting AP and PP were similar in both groups of dogs. At 4000 m, AP increased not significantly in controls, and decreased in denervated animals; PP increased in controls, but not in denervated dogs. It is concluded that integrity of the arterial chemoreceptor drive is essential in determining the eupneic level of ventilation and normal acid-base status of the blood in both resting and exercising dogs, at low and at high altitude, and in reducing the O2 circulatory requirement at high altitude. At 4000 m, the lack of carotid chemosensitivity is accompanied by severe hypoxemia, in association with hypercapnia and acidosis, and by increased cardiac blood flow, most presumably due to decreased peripheral resistance and increased venous return; despite these compensatory changes in circulatory O2 convective transport, denervated animals reach a maximum O2 uptake at lower work load than controls.