Conscious newborns of 12 species from 4 mammalian orders, ranging in body mass (M) from 1 g (mouse) to 5 kg (deer), were studied during air and during 5% CO2 breathing. The interspecies relationship between oxygen consumption (VO2) and M was the same in air and hypercapnia, in both cases VO2 alpha M 0.90; on average, hypercapnic VO2 was 101% of the air value. In 5% CO2, ventilation (VE) increased in all newborns, mostly because of the increase in tidal volume (178%), whereas breathing rates averaged 98% of the air values. The hyperpnea during CO2 was slightly greater in the larger newborns. Body temperature was not altered by CO2 breathing. We conclude that the average respiratory response of the newborn to moderate hypercapnia is a hyperventilation different from that of the neonatal mammal in acute hypoxia (Mortola et al., Respir. Physiol. 78: 31-43, 1989). In fact, hypercapnic hyperventilation resulted only from the hyperpnea, with no hypometabolic contribution, and the hyperpnea reflected the increase in tidal volume, with no change in rate. It is also concluded that the neonatal hypometabolic response is specific to hypoxia, and not an undifferentiated response to chemoreceptors stimulation.