The interaction between craniofacial structure assessed by lateral cephalometry, and tongue, soft palate, and upper airway size determined from computed tomography (CT) scans was examined in 25 control subjects and 80 patients with obstructive sleep apnea (OSA). On the basis of the cephalometric analyses, the patients with OSA had retruded mandibles with larger ANB angle differences, elongated maxillary and mandibular incisors and mandibular molars, and high total upper and lower face heights The computed tomographic evaluations revealed that patients with OSA also had larger tongue, soft palate, and upper airway volumes. Men with OSA and skeletal Class I malocclusions had significantly larger soft palates than comparable controls. Both tongue and soft palate volumes were positively correlated with body mass index. A principal component analysis reduced the database, and one significant correlation was identified. Subjects with high total, upper and lower face heights, elongated maxillary and mandibular teeth, and proclined lower incisors were observed to have large tongue, soft palate, and upper airway volumes, to have a higher apnea index and to be obese. Linear regression analysis indicated that a high apnea index was seen in association with large tongue and soft palate volumes, a retrognathic mandible, an anteroposterior discrepancy between the maxilla and mandible, an open bite tendency between the incisors, and obesity.