Recently, we have described the effects of hypoxia and of hypercapnia on the metabolic (VO2) and ventilatory responses to cold in unanesthetized intact and carotid body-denervated (CBD) rats (Gautier et al., J. Appl. Physiol. 73: 847-854, 1992 and 75: 2570-2579, 1993). In the present paper, we have reanalyzed the above results for a more detailed study of the interactions of hypoxia (FIO2 = 0.12), hypercapnia (FICO2 = 0.04) and changes in VO2 with the ventilatory control. The results show that: (1) Compared to normoxia, in hypoxia increments in V and VT are proportional to VO2 whereas in hypercapnia increments in ventilation (V) and tidal volume (VT) are independent of VO2. In both hypoxia and hypercapnia, increases in respiratory frequency (fR) are independent of VO2; and (2) Interactions of hypoxia, hypercapnia and VO2 with control of V persist in CBD rats but, for a given VO2, V, VT and fR are lower than in intact rats. These interactions are essentially similar to those observed during muscular exercise performed in normoxia, hypoxia or hypercapnia. It is suggested that during cold exposure or muscular exercise, resulting both in increased VO2, there are common integrative structures probably located in the hypothalamus which are involved in the control of breathing.