To determine the effect of a single breath of 100% O2 on ventilation, 10 term (BW 3360±110g (SE); GA 39±.4 wk, postnatal age 3±.6days) and 10 preterm neonates (BW 2020±60 g, GA 34±2 wk, PNA 9±2 days) were studied during active and quiet sleep states. The single breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, FiO2 was adjusted to 16±0.6% for a control O2 saturation of 83±1%. After 1 minute of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. VE, VT, f, PAO2, PACO2, O2 saturation (ear oximeter) and TcPO2 were measured. VE always decreased with inhalation of O2 (p<0.01). In quiet sleep, the decrease in VE was less in term (14%) than in preterm (40%) infants (p<.001). Decrease in VE was due primarily to a drop in VT in term infants as opposed to a fall in f and VT in preterm infants (p<0.05). Apnea, as part of the response, was more prevalent in preterm than in term infants. In active sleep the decrease in VE was similar both among term (19%) and preterm (21%) infants (p>0.5). These results suggest greater peripheral chemoreceptor response in preterm than in term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in term infants.