Although the occlusal vertical dimension (OVD) is strictly controlled, the neuronal mechanism of its regulation is still unclear. We hypothesize that neurons in the trigeminal mesencephalic nucleus (MesV) play an important role in the regulation of the OVD, because the MesV receives the projection from jaw-closing muscle spindles and periodontal mechanoreceptors. We measured the temporal OVD change in the guinea pig to study the effects of MesV lesions on the OVD. OVD-raised animals without MesV lesions showed a rapid OVD decrease to the same level as that in naïve controls, followed by an OVD increase after the OVD-raising appliance was removed. In contrast, OVD-raised animals with MesV lesions showed only a slight decrease in the OVD for 15 days after removal of the appliance, and then the OVD increased. The time-course of OVD development in normal-bite animals with MesV lesions was similar to that of naïve controls. These results suggest that MesV neurons are involved in OVD regulation.