In a sample of 25 adult male subjects with moderate to severe obstructive sleep apnea, the interaction among craniofacial, airway, tongue, and hyoid variables was quantified by means of a canonical correlation analysis. One lateral cephalometric radiograph with the teeth in occlusion was obtained for each subject together with overnight polysomnographic measurements before the initiation of therapy. A principal component analysis reduced the data base and one significant canonical correlation (r1 = 0.994) was identified for the 22 variables. Sleep apnea subjects showed a posteriorly positioned maxilla and mandible, a steep occlusal plane, overerupted maxillary and mandibular teeth, proclined incisors, a steep mandibular plane, a large gonial angle, high upper and lower facial heights, and an anterior open bite in association with a long tongue and a posteriorly placed pharyngeal wall. A multivariate statistical analysis extracted clinically significant associations among craniofacial, tongue, and airway variables. Subjects with sleep apnea demonstrated several alterations in craniofacial form that may reduce the upper airway dimensions and subsequently impair upper airway stability.