['To determine whether combined pre- and postnatal nicotine exposure compared with prenatal exposure alone results in more compromised postnatal hypoxia defense mechanisms and further alteration of the postnatal breathing pattern (reduced tidal volume and increased respiratory rate).', 'Seven lambs exposed to nicotine prenatally (pN) (approximate maternal dose: 0.5 mg/kg/d) and seven lambs exposed to nicotine pre- and postnatally (ppN) (postnatal dose: 1.6-2 mg/kg/d) were studied without sedation at an average age of 5 d and 21 d during resting (room air) conditions, during exposure to 10% O2 and during a brief exposure to 100% O2.', 'Resting minute ventilation, occlusion pressure, effective impedance, heart rate and mean arterial blood pressure were similar in the two groups during wakefulness and quiet sleep. Resting tidal volume was significantly higher in ppN than in pN lambs during wakefulness (9.4 +/- 0.7 vs 7.7 +/- 1.4 ml/kg, p < 0.05) and quiet sleep (9.8 +/- 0.6 vs 7.6 +/- 1.5 ml/kg, p < 0.01) at 5 d and also at 21 d during wakefulness (7.7 +/- 1.0 vs 6.2 +/- 1.1 ml/kg, p < 0.05). The ventilatory, heart rate and blood pressure responses to hypoxia were comparable in the two groups during both activity states. Time to arousal from quiet sleep in response to hypoxia was equivalent in the two groups. The ventilatory response to hyperoxia was not significantly different in the two groups during either activity state.'] Does postnatal nicotine exposure further compromise hypoxia defense mechanisms in prenatally nicotine-exposed lambs?