The cranial base and whole mandible of 7-day-old mice were cultured for 1 or 2 weeks in a novel organ culture system that provided an articulating movement for the temporomandibular joints. The mandibles were articulating either in a closed or in an open position to simulate the in vivo mouth-breathing pattern. The reactions of the condylar processes were followed macroscopically and microscopically after osteoid or von Kossa staining. After 1 week of culture, small differences were found in the shape of the condylar processes between the two groups. After 2 weeks, significantly increased growth was observed superiorly in those condyles which had been working in a closed position and posteriorly in the condyles which had been working in an open position. Histologic analysis revealed that after 1 week calcification had proceeded faster in the posterior aspect of the condyles in the mandibles which had been working in a closed position as compared to the mandibles which had been working in an open position, and the difference was even more marked after 2 weeks. In the latter condyles calcification had proceeded markedly in the anterosuperior aspect. Osteoid staining showed that perichondrial mesenchymal cells had differentiated into osteoblasts in the posterior aspect of the condyles in those mandibles which had been working in a closed position. This led to a ceasing of expansive growth in the posterior aspect and thus to a more upwardly directed condylar growth. In mandibles which had been working in the open position to simulate the mouth-breathing pattern in vivo, chondrogenesis and thus expansive growth continued in the posterior aspect, leading to a more posteriorly directed condylar growth. We tried to simulate in a novel organ culture system the in vivo functional pattern where the mandible is lowered anteriorly as, for instance, in association with mouth-breathing.This led to a more posteriorly directed condylar growth as compared to control mandibles which had been functioning in a more closed position.The histologic findings after osteoid staining support the assumption that the differentiation of the mesenchymal cells in the anterior and posterior aspect of the condyle either into osteogenic or chondrogenic cells, depending on the position of the condyle in the fossa, has a role in the adaptive mechanism. The differentiation seems to be regulated by maturation of the cartilage which further is regulated by articulating function.