SummaryTo examine the influence of feeding on the chemical control of breathing in neonates, we studied the ventilatory response to 3% CO2in air in nine bottle fed (BOT) and eight breast fed (BR) term infants during feeding while the infants were alert. Control responses were obtained either before or after feeding. &OV0312;E, respiratory frequency, tidal volume, inspiratory time, expiratory time, and sum of inspiratory and expiratory time, VT/Ti, Ti/Ttot, PACO2and slope (S) of CO2response (liter/min/kg/mmHg) were determined. During 3% CO2while resting BR had a lower &OV0312;E, VT, VT/ Ti than BOT and S in BR was 40% of BOT (P< 0.05). During feeding and CO2when compared to resting and CO2there was no difference in either BR or BOT in VT/Ti but Ti/Ttotdecreased in both groups. During feeding, S in BOT was reduced from 0.049 ± 0.012 (mean ± S.E.) to 0.013 ± 0.002 (74% reduction) and in BR from 0.020 ± 0.002 to 0.009 ± 0.002 (55%). Thus, behavioral activity (either BR or BOT) markedly depresses the ventilatory response to chemical stimuli (CO2). This modification is primarily related to changes in “effective” respiratory timing (Ti/Ttot) rather than mean inspiratory flow (VT/Ti).SpeculationThis is the first demonstration in the newborn infant that behavioral activity (feeding) can override the usual ventilatory control mechanisms. The precise mechanism is unknown and requires further study.