The perikarya of sensory neurons of the mesencephalic trigeminal nucleus (MTN) receive dense histaminergic hypothalamic innervation. In this study, we examine the yet unknown expression and localization of histamine receptors in the rat MTN using immunohistochemistry with subtype-specific antibodies. Same as the masticatory muscle spindle somata H1 receptors were located along the entire MTN, whereas H3 receptors were detected in the caudal pontine part of the nucleus, which receives input from periodontal afferents. Most of the immunostained cell bodies were surrounded by histidine decarboxylase-, histamine- or vesicular monoamine transporter 2-containing pericellular varicose fibers and terminals in a basket-like manner. Our results suggest that rat MTN neurons are directly influenced by histaminergic descending projections from the hypothalamus. It can be inferred that processing of proprioceptive information at the level of the MTN is controlled via histamine H1 and H3 receptors through different postsynaptic mechanisms.