In order to evaluate the effects of epinephrine on the cardiorespiratory response to hypoxia in the neonate, 35 sedated, spontaneously breathing newborn piglets (mean +/- SD, age 5 +/- 0.8 days; weight 1.6 +/- 0.3 kg) with intact (ICB) or denervated (DCB) carotid bodies were studied before and during an infusion of saline or epinephrine (2.2 +/- 1.0 microgram/kg/min, i.v.). Cardiorespiratory measurements were performed while the animals breathed room air and after 10 min of hypoxia (FiO2 0.10) during saline or epinephrine infusion. During epinephrine infusion, the ICB animals had a sustained increase in minute ventilation during hypoxia while the control group showed a biphasic ventilatory response with depression during sustained hypoxia. After the chemodenervation, the ventilatory response to hypoxia was completely blunted in saline and epinephrine animals. In the ICB and DCB animals, the arterial blood pressure decreased significantly with hypoxia during epinephrine infusion, while cardiac output increased significantly in all ICB and DCB saline animals. The oxygen consumption (VO2) decreased significantly after 10 min of hypoxia in all groups except in the ICB epinephrine animals, in whom the VO2 did not change with hypoxia. In conclusion, the administration of epinephrine to newborn piglets reverses the depressed ventilatory response to hypoxia and this effect requires the activity of the peripheral chemoreceptors.