The ventilatory effects of inspiratory flow-resistive loading and increased chemical drive were measured in ten neonates during progressive hypercapnia in control and loaded states. Hypercapnia (mean increase PCO2 = 15-20) resulted from inspiring 8% CO2 in room air and inspiratory loading by a flow-resistive load = 100 cmH2O X l-1) X s. Hypercapnia produced an increase in group minute ventilation secondary to increasing tidal volumes and breathing frequencies. Loading shifted the minute ventilation-CO2 response to the right, and slopes decreased significantly (P less than 0.05) consequent to a significant decrease in the frequency-CO2 slopes (P less than 0.05), which became negative in four of the ten subjects. Mouth pressure measured at 100 ms after onset of inspiratory effort (P100) occlusion pressure-CO2 slopes measured in five subjects showed no significant increase with load application. Resistive loading produced significant increases in inspiratory time (P less than 0.02) and the inspiratory time/total breath time ratio (P less than 0.01). Airway occlusion elicited the Hering-Breuer reflex, with a significant increase in inspiratory time-to-total breath time ratio (P less than 0.01). The results show that the inspiratory resistive load produced ventilatory compromise in newborns and insufficient compensatory augmentation of central drive.