We studied the relationship of sudden unexpected infant death/apparent life-threatening events (ALTE) to obstructive sleep apnea (OSA) in 74 index probands who had either sleep-laboratory-confirmed OSA or a clinical diagnosis of OSA requiring treatment, 62 matched control probands, and their spouses and first- and second-degree relatives. Sleep was monitored in the home overnight, and OSA was defined by respiratory disturbance indices (number of apneas/hypopneas per hour of sleep) corrected for normal increases with age. Information on sudden unexpected infant death/ALTE was obtained by questionnaire and was corroborated. For living relatives, data were obtained by questionnaire, examination, or study (cephalometric radiographs, ventilatory responsiveness to hypercapnia and hypoxia). Eight index families had 10 infants with sudden unexpected infant death/ALTE; two control families had three infants with sudden death (p = 0.11). All told, 91 of the 136 families (index plus control) included members with OSA, and all 10 infant death/ALTE families were among these (versus zero of 45 families with no OSA; p = 0.03). The sudden infant death/ALTE families had a greater frequency of two or more members with OSA (p = 0.06), reported more respiratory disease or allergy, were more frequently brachycephalic (p = 0.05), and had a smaller mean posterior nasal spine-basion distance (p = 0.0001) and ratio of anterior mandibular/anterior maxillary dental height (p < 0.05). Ventilatory responses to hypoxia were reduced in members of families with OSA (p = 0.008), with a trend toward the greatest blunting in subjects from families with OSA plus sudden unexpected infant death/ALTE. Thus, OSA in adults and sudden unexpected infant death/ALTE in their biologic relatives appear to be related. Familial factors influencing this association may include the degree of the predilection for OSA, liability for respiratory illness or allergy, dimensions of the oral-pharyngeal airway, and ventilatory response to hypoxia.