To learn whether the ventilatory responses to hypoxia (17% O2) and hypercapnea (4% CO2) differ in the subsequent siblings of sudden infant death victims (SIDS), we studied seven normal control infants, nine infants who had had a prolonged apneic spell (apneic infants), and 10 subsequent siblings of SIDS (mean ages 10.4 weeks, 15 weeks, and 10 weeks, respectively). With inhalation of 17% O2, one of seven controls, two of nine apneic infants, and seven of 10 siblings of SIDS breathed periodically (controls vs siblings, P less than 0.04). Heart rate and end-tidal PCO2 did not change, but respiratory rate decreased in the siblings (45 to 31 breaths per minute, P less than 0.001). Arousal occurred during 25% of the hypoxic challenges in the controls and apneic infants but was not seen in the siblings of SIDS (control vs siblings P less than 0.08, apneic vs siblings P less than 0.05). With inhalation of 4% CO2 there was a similar increase in estimated ventilation among the three groups. Arousal occurred 33% of the time in all three groups. Our findings show that, after 5 weeks of age, siblings of SIDS have a normal response to hypercapnea but respond to mild hypoxia with periodic breathing.