SUMMARY1. The ventilatory response to square-wave challenges in end-tidal partial pressure of CO2 (Pc02) was investigated at three levels of arterial Po0 (Pa°2) 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 ofnormoxaemia (Pa°2 = 12 70 +0O72 kPa, mean + S.D.), fifty-three against a background of moderate hypoxaemia (Pao = 8-63 +034 kPa) and fifty-one against a background of severe hypoxaemia (Pa,02 = 4-98 +030 kPa).4. The sensitivity of the peripheral chemoreceptors in mediating the response to C02 increased from 38-3 + 17-0 ml min-kPa-1 kg-1 during normoxaemia to 48-8 + 15-3 ml min-kPa-1 kg-' 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 (1040± 39-0 and 1008 + 41 6 ml min' kPa-1 kg-', respectively) it decreased to 85 9 + 54-1 ml min-' 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 C02 sensitivity centrally.