The mast cell, an immunocompetent cell that contributes to neurogenic inflammation in a variety of tissues, including synovium, is found in close proximity to peripheral terminals of unmyelinated primary afferents and sympathetic postganglionic nerve terminals. In this study we evaluated the hypothesis that the density of mast cells in synovial tissue is dependent on the neural innervation. In normal rats, we found that the density of mast cells in the ankle joint capsule, which is heavily innervated, is greater than in the capsule of the knee, which is less densely innervated. Selective lesions of unmyelinated primary afferents with capsaicin, or of sympathetic postganglionic neurons with guanethidine, produced a significant decrease in mast cells; surgical removal of the parasympathetic ganglia did not significantly affect mast cell density. Finally, the number of mast cells in the synovial joint of spontaneously hypertensive rats, which have increased sympathetic activity, was significantly greater than in normotensive control rats. These observations support the hypothesis that the innervation in the synovial joint of the rat, by unmyelinated afferents and sympathetic efferents, exerts a trophic effect on mast cell density.