The purpose of this study was to identify and quantify the temporal sequence of replicating mesenchymal cells during natural growth and mandibular advancement in the condyle and the glenoid fossa. One hundred fifty 35-day-old female Sprague-Dawley rats were randomly divided into 10 experimental groups (10 rats each) and 10 control groups (5 rats each). The experimental groups were fitted with appliances that positioned the mandible forward. One hour before the rats were killed, bromodeoxyuridine (BrdU) was intravenously injected into them. Sections were cut and stained with anti-BrdU antibody to evaluate the number of replicating mesenchymal cells. Cellular uptake of BrdU was quantified with the Leica Qwin (Leica Microsystem Imaging Solutions, Cambridge, United Kingdom) system. The results showed that the numbers of replicating mesenchymal cells during natural growth were highest in the posterior region of the condyle and the anterior region of the glenoid fossa. In the experimental groups, the posterior region had the highest number of replicating cells for both the condyle and the glenoid fossa, with the condyle having 2 to 3 times more replicating cells than the glenoid fossa. The number of replicating mesenchymal cells, which is genetically controlled, influences the growth potential of the condyle and the glenoid fossa. Mandibular protrusion leads to an increase in the number of replicating cells in the temporomandibular joint. Individual variations in the response to growth modification therapy could be a result of the close correlation between mesenchymal cell numbers and growth.