We investigated in conscious rats the characteristics and modes of action of CO2 on thermoregulation and ventilatory control during cold stress. In a group of 10 rats studied intact and after carotid body denervation, measurements of metabolic rate (VO2), ventilation (V), shivering, and colonic temperature (Tc) were made at controlled ambient temperatures (Ta) of 25, 20, 15, 10, and 5 degrees C. Animals were exposed on different days to 1) normoxia, 2) normoxia and 4% CO2, 3) 12% hypoxia, or 4) 10.8% hypoxia and 4% CO2. The following results were obtained. 1) During CO2 exposure in normoxia or hypoxia, VO2 is increased at Ta of 25 degrees C and decreased for lower Ta. These effects are partly mediated by carotid body afferents. 2) Shivering and nonshivering thermogenesis and therefore Tc regulation are affected by CO2 exposure as shown by relationships between VO2-Tc and VO2-shivering intensity. 3) V is controlled by PO2 and PCO2 directly through their peripheral and central actions but also indirectly through their effects on VO2. Our conclusions are as follows. 1) Control of Tc is markedly dependent on PCO2 level. Carotid body afferents play a role, but direct central effects acting on the different sources of thermogenesis and possibly on thermolysis are most prominent. 2) As far as control of V is concerned, during hypercapnia in normoxia or hypoxia, several analogies may be formed between exposure to cold and muscular exercise, both of which increase VO2 and V, suggesting common integrative mechanisms at the central nervous system level.