Prevalence of sleep-disordered breathing (SDB) is reported to increase in menopausal women. We examined response to a nocturnal respiratory challenge (nasal occlusion) during overnight polysomnography in 31 women (45 to 55 yr). Thirteen were premenopausal, four perimenopausal, and 14 postmenopausal by history and hormonal assay. Nasal occlusion increased the apnea hypopnea index (AHI) (occlusion mean = 6.6 +/- 8.0 versus baseline mean = 1.6 +/- 2.6, p < 0.01) and arousal index (occlusion mean = 35.1 +/- 20.1 versus baseline mean = 20.7 +/- 11.6, p < 0.001), but did not change the oxygen saturation nadir in those with respiratory events (occlusion mean = 91.8 +/- 4.2 versus baseline mean = 92.0 +/- 11.6). Menopausal groups did not differ on AHI, arousal index, or oxygen saturation nadir in either condition. Key variables were compared between occlusion responders (n = 11) and nonresponders (n = 20). Responders and nonresponders were not distinguished by age, menopausal status, nor several cephalometric or anthropometric variables. Body mass index (31.1 +/- 8.5 versus 24.3 +/- 3.4, p < 0.003), neck circumference (34.0 +/- 2.5 versus 32.5 +/- 1.7 cm, p < 0.05), and mandibular-hyoid distance (18.5 +/- 3.8 versus 14.5 +/- 5.7 mm, p < 0.05) were greater in responders. These findings suggest hormonal factors may be less important than weight and facial morphology in midlife development of SDB in women.