The rat and guinea pig are widely used in experimental models dealing with immuno allergic bronchoreactivity. The present study was designed to compare the distribution and heterogeneity of the mast cell population in the respiratory tract of the Sprague-Dawley rat and Hartley guinea pig. Mast cells were identified according to the sequential Alcian blue/safranin O staining method. From the trachea to the peripheral conductive airways, the density of mast cells increased in the guinea pig whereas it decreased in the rat. Although mast cells were observed in the interalveolar septa of the guinea pig, none were found in the rat. In the lung of the rat, three types of mast cells were observed: in the wall of the trachea and large bronchi, safranin-positive, mixed and Alcian-blue-positive mast cells were found, whereas only Alcian-blue-positive mast cells were observed in the small conductive airways. In contrast, only Alcian-blue-positive mast cells were observed in the lung of the guinea pig. These results show that the types and localization of the mast cell populations are distinctly different in these two species. Consequently, experimental models of bronchoreactivity in these species are testing different cellular systems.