Connective tissue mast cells (CTMC) and mucosal mast cells (MMC) are apparently different, but the ontologic relationship between these two types of mast cells was unclear. We investigated the relationship by combining in vivo and in vitro techniques. Although bone marrow-derived mast cells developed in suspension culture resemble MMC, they acquired histochemical, electron microscopical, biochemical and immunological characteristics of CTMC after the transfer into the peritoneal cavity of genetically mast cell-deficient WBB6F1-W/Wv mice. On the other hand, when single peritoneal mast cells (typical CTMC) of WBB6F1-+/+ mice were injected into the stomach wall of WBB6F1-W/Wv mice, CTMC appeared in the muscularis propria and MMC in the mucosa. These results suggest that CTMC and MMC may interchange and that their phenotypes are determined by the anatomical microenvironment in which the final differentiation occurs.