The differences in the immediate (30 sec or l min) and late (5 min) ventilatory response to high and low O2have not been quantitated in preterm infants and adult subjects using the same methods. It was thought that these differences might explain the paradoxical ventilatory response to CO2at various O2concentrations in preterm infants (12). Thus, 9 preterm infants and 10 adult subjects were given 21% O2to breathe and then 100 or 15% O2for 5 min each. Adults also breathed 15% O2before 100% O2or 12% O2in order to make their resting arterial PO2more comparable to those of infants breathing 21% O2. The ventilatory response to 100% O2was the same in preterm infants and adult subjects, but the late response to 15% O2remained paradoxical, ventilation decreasing at 5 min by 18% in infants and increasing by 19% in adults. The authors conclude: 1) the traditional concept of the ventilatory response to 100% O2being different in infants and adult subjects is false; 2) the notion that the response to low O2is paradoxical in infants is correct; and 3) the data do not explain why the response to CO2under various background concentrations of O2in infants is the reverse of that in adult subjects, but the depressed ventilatory response to hypoxia in infants may justify, at least in part, their flatter response to CO2during low O2breathing.Speculation The findings suggest that the response of preterm infants to high and low O2per se is not the cause of the paradoxical response to CO2under various background concentrations of O2. If it were, it would be expected that the response to low and high O2would differ in infants and adults. This was true for hypoxia only, the response to hyperoxia being the same in infants and adults. The speculation, therefore, is that differences in cerebral blood flow caused by CO2and O2interaction may be responsible for the paradoxical response to CO2.