In this study, three series of experiments were conducted on euthermic, anesthetized, artificially ventilated golden mantled ground squirrels (Spermophilus lateralis), each of which altered pHa in a different fashion. In Series I, animals were randomly hypo- or hyper-ventilated. On average, pHa changed from 7.13 to 7.59, PaCO2 from 59.2 to 23.6 Torr, and PaO2 from 45.8 to 57.2 Torr between the two conditions, respectively. VO2 showed a significant positive correlation with pHa (r = +0.84) as well as PaO2 (r = + 0.60). In Series II, respiratory acidosis was produced by pump-ventilating animals with up to 10% inspired CO2 to reduce pHa to within the range 7.40 to 7.20. On average, pHa was reduced to 7.30, PaO2 to 50.1 Torr and PaCO2 was increased to 56.7 Torr. As in Series I, there was a significant positive correlation between VO2 and pHa (r = +0.78) and between VO2 and PaO2 (r = +0.71). In Series III, metabolic acidosis was produced by infusing lactic or acetic acid intravenously for 20 to 30 min. This reduced pHa from 7.56 to 7.32, PaO2 from 70.2 to 58.9 Torr, and elevated PaCO2 from 26.9 to 37.9 Torr (P < 0.05 in all cases). Contrary to Series I and II, VO2 increased with a decline in pHa (r = -0.65, P < 0.05) and PaO2 (r = -0.55, P < 0.05). Thus, despite a significant decline in pHa and PaO2 and an elevation of PaCO2 during all three series, VO2 changed in opposite directions during respiratory and metabolic acidosis. We conclude that whatever the mechanism involved, hypoventilation during the early stages of entrance into hibernation can contribute to the fall in metabolic rate.