The effects of prenatal (embryonic days 7-21) cocaine (30 mg/kg b.i.d., s.c.) exposure on postnatal respiratory and behavioral responsiveness to acute hypoxia were investigated in 5-day-old (P5) rat pups. Control and cocaine-exposed pups were subjected to 20 min of 0.21 FIO2 followed by 20 min of 0.08 FIO2. Although all pups demonstrated the characteristic biphasic response to hypoxia, cocaine-exposed pups exhibited a blunted, initial response in minute ventilation (p < 0.05) and inspiratory drive (p < 0.05) as compared with control pups who showed increases in these measures (p < 0.01 and p < 0.05, respectively). The consequence of this apparent blunted ventilatory response was reflected in blood gas data gathered after 20 min of 0.08 FIO2:PCO2 (p < 0.05) and base-excess (p < 0.05) were increased and HCO3- (p < 0.05) and SO2 (p < 0.01) were decreased relative to control pups. Cocaine-exposed pups also exhibited behavioral evidence of decreased struggling (p < 0.001) in response to the hypoxic challenge. These data in the rat confirm our previous findings of altered ventilatory responsiveness to inspired hypoxia in the rabbit and extend our observations of a decreased ability to successfully compensate and behaviorally arouse following prenatal cocaine-exposure, thus underscoring the potential vulnerability of infants so exposed.