Several studies have emphasized the role of familial factors and familial aggregation in increasing susceptibility to obstructive sleep apnea syndrome (OSAS); the aim of the present study was to investigate the possible influence of human leukocyte antigen (HLA) in the development of sleep disordered breathing and OSAS of children. Between January 2000 and January 2003, all the 370 children [193 males; median age: 5.2 years (range: 1-12 years)] with sleep disordered breathing referred to our Center were screened by a 41-item multiple-choice questionnaire. All habitual snores children underwent a polisomnographic evaluation, and those with an apnea/hypopnea index >3 were diagnosed as having OSAS. All children with OSAS or primary snoring were HLA typed for class I and II. According to nocturnal polygraphic monitoring study, 41 patients were diagnosed as having OSAS and 32 as primary snoring. Patients in the two diagnostic groups were homogeneous for demographic and clinical characteristics. HLA-B65 was found to be significantly more expressed in children with sleep disordered breathing as compared with controls (10.5% versus 3.61; Pypc < 0.04) while no difference was found for the other tested antigens. A logistic regression analysis found cough (P < 0.02) and persistent wheeze (P < 0.008) the sole risk factors for OSAS development. Our preliminary data suggest that HLA does not play a key role in the pathogenesis of OSAS, however more studies are needed to clarify this issue.