We studied the neuroimmunomodulatory effect of capsaicin on the development of delayed-type hypersensitivity (DTH) reaction and antibody formation after reduction of neuropeptides in the peripheral sensoric nervous system. Rats were sensitized with picryl chloride on their shaved abdomen or by subcutaneous injections with picrylsulfonic acid (PSA). Manipulation of the content of neuropeptides in the sensory nerve system with capsaicin was performed 1 week before or after sensitization. An increase of the DTH reaction assessed as increased ear thickness after challenge was seen especially when the rats were given capsaicin after sensitization. The formation of specific antibodies was not affected, although the level of total IgG was decreased in PSA-sensitized rats treated with capsaicin after sensitization. The results demonstrated that the DTH reaction in rat was slightly but significantly affected by the abolishment of neuropeptides in sensoric nerve endings with capsaicin. Even if the direct effect of capsaicin on the immune system still has to be elucidated, these results indicate that neuropeptides in sensory nerves are involved in the pathogenesis of DTH.