In the correction of large sagittal discrepancies in the relationship between the maxilla and the mandible, the orthopedic effect of treatment is often of small magnitude when compared with the dentoalveolar changes. A group of patients with severe Class II malocclusions were treated to assess the effects of a therapeutic approach which specifically took into consideration important factors such as type of anchorage, amount of force, age at start of treatment, and intensity of treatment to obtain the maximal orthopedic improvement. A special headgear-Herbst appliance was designed and short intensive treatment, lasting 5 months, was performed in the very early mixed dentition. Comparison with an untreated control group revealed the dramatic effects of treatment. The overall average change in the sagittal relationship between the maxillary and mandibular teeth was 7.5 mm after active treatment. The posteriorly directed effect on the maxilla of 3.1 mm was due to a combination of distal movement of the dentoalveolar arch and of posterior translation of the basal portion of the maxilla. The anteriorly directed effect upon the mandible of 4.4 mm was due mostly to anterior movement of the basal part of that bone, with a small part resulting from labial movement of the lower incisors. This appeared to be the result of a stimulation of growth of the mandibular condyles, a change in mandibular morphology, and an anteroinferior change in position of the condyles with a possible anterior translation of the glenoid fossa. After a 10-month posttreatment period during which an activator was used during the initial 6 months, a new comparison between the treated group and the control group was made. Growth continued to the same extent in the treated group as in the control group. However, a tendency toward relapse in overjet of 2.3 mm was observed, leading to some modifications in the treatment approach in recently started cases. A short period of interceptive orthopedic treatment in the very early mixed dentition may be indicated to correct skeletal deviations and establish a normal relationship between the maxilla and the mandible. Treatment could then be followed by a period without appliance wear until final dentoalveolar adjustments, if necessary, are made in the permanent dentition.