The hypothesis that postnatal nicotine exposure weakens cardiorespiratory recovery from reflex apnea and bradycardia was tested in eight lambs continuously infused with nicotine from the day of birth at a dose of 1 to 2 mg·kg Ϫ1 ·d Ϫ1 . Eight age-matched lambs infused with saline served as controls. Apnea and bradycardia were elicited by laryngeal stimulation with 1 mL of water (laryngeal chemoreflex) both during air breathing [0.21 fraction of inspired oxygen (FiO 2 )] and mild hypoxia (0.10 FiO 2 ) at a mean postnatal age of 5 Ϯ 1, 14 Ϯ 1, and 28 Ϯ 1 d. Ventilation, heart rate, and blood pressure were similar in the two groups at rest. In response to laryngeal chemoreflex stimulation, nicotine-treated lambs had a more pronounced decrease in ventilation (p Ͻ 0.05), longer reflex apnea (p Ͻ 0.001 in 0.21 FiO 2 ; p Ͻ 0.01 in 0.10 FiO 2 ), and greater reflex bradycardia (p Ͻ 0.01). During reflex apnea, sighs were less efficient in restoring heart rate to prestimulation level, and a greater decrease in heart rate was observed before sighs in nicotine-treated lambs. These effects were most apparent at 5 d of age, when nicotine-treated lambs also had lower ventilation during hypoxia (p Ͻ 0.05). The response to hyperoxia was comparable in the two groups at all ages. The ability to terminate laryngeal chemoreflex-induced apnea is attenuated in young lambs continuously exposed to nicotine. This attenuation is present both in normoxia and in hypoxia and is accompanied by reduced effects from sighing on cardiac autoresuscitation. Laryngeal stimulation with fluids potentially harmful to the airways induces a graded and reproducible reflex response consisting of laryngeal constriction, swallowing, and apnea followed by hypoventilation (1). The inhibition of respiration is accompanied by a cardiovascular response consisting of bradycardia, peripheral vasoconstriction, and redistribution of blood flow (2, 3). This response may be particularly strong in young mammals and lead to cardiovascular collapse and death (4). Termination of LCR apnea relies on mechanisms similar to those that modulate the cardiorespiratory response to hypoxia, i.e. sympathetic activation, increased alertness, and augmented peripheral chemoreceptor and baroreceptor sensory discharge. The clinical importance of these escape and defense mechanisms are supported by observations that infants who are at risk for life-threatening events are also less able to recover from LCR-induced reflex apnea and bradycardia (5,6) In this study, we tested the hypothesis that long-term postnatal exposure to nicotine attenuates and prolongs recovery from apnea and bradycardia in response to LCR stimulation. This notion was based on our previous observations that postnatal nicotine exposure leads to an attenuation of cardiorespiratory defense mechanisms to hypoxia (7). We therefore assumed that nicotine, which has effects on both sympathetic regulation and the ventilatory response to hypoxia, could adversely affect cardiorespiratory recovery from induced apnea.