The pathogenic mechanisms responsible for the development of lesions in swine and mice after infection with Treponema hyodysenteriae have not been fully characterized. The release of inflammatory mediators from mast cells has been postulated to play a role in lesion development during swine dysentery. Therefore, C3H/HeN mice were infected with T. hyodysenteriae, and mucosal mast cell (MMC) numbers were examined in cecal sections. An initial increase in MMC numbers from 13 to 22 per 50 crypt villus units was observed, but at 20 days postinfection the numbers significantly decreased (P less than 0.05) to 5 MMC per 50 crypt villus units. Immunohistochemical analysis performed on cecal sections failed to show a significant change in lamina proprial T-lymphocyte subsets. Numbers of T. hyodysenteriae CFU recovered from the cecum were stable throughout the experimental time period. Mast cell-deficient W/Wv mice and their mast cell-sufficient littermates were also infected to determine whether MMCs were necessary for the occurrence of T. hyodysenteriae-induced lesions. W/Wv mice were as susceptible to infection as their normal littermates and developed similar macroscopic and microscopic lesions. These results indicate that changes in MMC numbers can be detected after an infection with T. hyodysenteriae; however, on the basis of observations of infected W/Wv mice, mast cells are not required for lesion development in the murine model.