Experiments were carried out on rat pups to investigate the interaction between prenatal exposure to nicotine and postnatal age on protective responses that promote survival during exposure to hypoxia. From days 6 or 7 of gestation, pregnant rats received either nicotine (approximately 6 mg of nicotine tartrate/kg of body weight per day) or vehicle continuously via a 28-day osmotic minipump. On postnatal days 1--2, 5--6 and 10--11, the pups were exposed either to a single period of hypoxia produced by breathing an anoxic gas mixture (97% N(2) and 3% CO(2)) and their time to last gasp determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea determined. Prenatal exposure to nicotine decreased the time to last gasp, but only in the 1--2-day-old animals. The total number of gasps was, however, increased in this age group due to the effect of nicotine on the gasping pattern. Furthermore, prenatal exposure to nicotine decreased the number of successful autoresuscitations and influenced the cardiorespiratory events preceding death in the 1--2- and 5--6-day-old pups but not in the 10--11-day-old pups. Thus, our experiments show that prenatal exposure to nicotine impairs protective responses of rat pups that may sustain life during exposure to hypoxia in an age-dependent manner.