The response of the soft-tissue profile to retraction of the maxillary incisors is still a matter of controversy. The purpose of this study was to improve the clinician's ability to predict the soft-tissue profile changes caused by retraction of the maxillary incisors by quantifying the profile changes, and identifying and quantifying the contribution of the most significant factors responsible for these changes. The cephalometric records of 80 Class II, Division 1 treated female subjects and 53 untreated female subjects were digitized and analyzed by means of a stepwise multiple regression analysis. The statistical assessment of the data suggested the following conclusions: In general, growth was associated with only minimal changes in the soft-tissue profile in a period not exceeding 36 months. The three clinically significant soft-tissue changes occurring in response to orthodontic treatment that included a mean upper incisor retraction of 6.7 mm were the retraction of the upper lip, the increase in the lower lip length, and the increase in the nasolabial angle. Other soft-tissue changes, which were of little clinical significance, included the retraction of the lower lip, the reduction of the interlabial gap, the increase in the thickness of both the upper and lower lips, the increase in the soft-tissue lower facial height and the lower soft-tissue component, which is the distance between lower stomion and soft-tissue menton. The length of the upper lip did not increase with either growth or orthodontic treatment. In general, changes in the lower lip in response to orthodontic tooth movement were more predictable than those of the upper lip. The low degree of predictability associated with the upper lip response to orthodontic tooth movement may be caused by the complex anatomy and/or dynamics of the upper lip, which could not be evaluated by the presently available cephalometric techniques.