Previous studies of single families have suggested that familial factors may be important in the pathogenesis of obstructive sleep apnea. In this report, the role of inheritance in obstructive sleep apnea was assessed by quantitating the degree of familial clustering of symptoms associated with sleep-related breathing disorders. In total, 272 subjects from 29 families identified through an index case with obstructive sleep apnea and 21 control families with no relative known to have sleep apnea were studied with questionnaires that ascertained health status and symptoms. The unadjusted odds ratios of habitual or disruptive snoring, breathing pauses, and excessive day-time sleepiness in subjects with a single relative with the same symptom were 1.40 to 1.53 (p less than 0.05). Odds ratios increased progressively for subjects with increasing numbers of symptomatic relatives). Adjustment for body mass index, age, and gender modestly reduced these odds ratios to 1.33 to 1.42. These data suggest a significant familial aggregation of symptoms associated with sleep-disordered breathing that appears independent of familial similarities in weight.