1. The ventilatory response to square-wave challenges in end-tidal partial pressure of CO2 (PCO2) was investigated at three levels of arterial PO2 (Pa,O2) in nineteen anaesthetized 2- to 11-day-old piglets. 2. The ventilatory responses, measured on a breath-to-breath basis, were separated into a peripheral and a central component using a two-compartment model. Both components were described by a CO2 sensitivity, a time constant, a time delay and a single offset. 3. Fifty-six responses were analysed against a background of normoxaemia (Pa,O2 = 12.70 +/- 0.72 kPa, mean +/- S.D.), fifty-three against a background of moderate hypoxaemia (Pa,O2 = 8.63 +/- 0.34 kPa) and fifty-one against a background of severe hypoxaemia (Pa,O2 = 4.98 +/- 0.30 kPa). 4. The sensitivity of the peripheral chemoreceptors in mediating the response to CO2 increased from 38.3 +/- 17.0 ml min-1 kPa-1 kg-1 during normoxaemia to 48.8 +/- 15.3 ml min-1 kPa-1 kg-1 during moderate hypoxaemia and to 72.9 +/- 24.0 ml min-1 kPa-1 kg-1 at severe hypoxaemia. 5. As compared with the central CO2 sensitivity during moderate hypoxaemia and normoxaemia (104.0 +/- 39.0 and 100.8 +/- 41.6 ml min-1 kPa-1 kg-1, respectively) it decreased to 85.9 +/- 54.1 ml min-1 kPa-1 kg-1 at severe hypoxaemia. 6. We conclude that in newborn piglets there is a positive interaction between hypoxia and hypercapnia at the level of the peripheral chemoreceptors while severe hypoxaemia reduced the CO2 sensitivity centrally.