The aim of this study was to evaluate maxillary and mandibular shape/size changes by means of Bookstein's shape-coordinate and tensor analysis in children with Class III malocclusions treated with rapid maxillary expansion and a facial mask in order to define optimum timing of intervention for this type of therapy. The treated group (46 subjects, 26 females and 20 males) was divided into two subgroups according to the stage of dentitional development. The early-treated group consisted of 23 subjects treated in the early mixed dentition (mean age at Time 1, 6 years 9 months +/- 7 months); the late-treated group included 23 subjects treated in the late mixed dentition (mean age at Time 1, 10 years 3 months +/- 1 year). The mean treatment period was about 11 months. The control group (32 subjects with untreated Class III malocclusion, 18 females and 14 males) also was divided into two subgroups (an early control group, 17 subjects in the early mixed dentition, and a late control group, 15 subjects in the late mixed dentition). Maxillary triangles (point T, the most superior point of the anterior wall of sella turcica, point FMN, the fronto-maxillary-nasal suture, and point A) and mandibular triangles (point Condylion, point Gonion, and point Pogonion) were digitized on cephalograms in both groups at Time 1 and Time 2. Combined facial mask and rapid maxillary expansion therapy produced a significant enhancement of the forward growth of the maxilla and significantly more upward and forward direction of growth of the mandibular condyle (leading to smaller increments in mandibular total length, Co-Pg) in the early-treated group when compared with controls and to the late-treated group. Both maxillary size and mandibular size were significantly affected by treatment in the early mixed dentition. The results of this study indicate that orthopedic treatment of Class III malocclusion induces favorable size and shape changes both in the maxilla and mandible, and that this combined treatment approach is more effective in the early mixed dentition than in the late mixed dentition.