The strategic location of mast cells at the host-environment interface and their ability to release potent mediators of inflammation have suggested that these cells may play a pivotal role in host defense against bacterial infection. The ability of the opportunistic pathogen, Escherichia coli, to induce degranulation of mast cells obtained from the mouse peritoneum was investigated. We determined that unlike a mutant derivative deficient in the FimH subunit of the fimbriae or nonfimbriated E. coli, type 1 fimbriated E. coli induced mast cell degranulation in vitro. The magnitude of mast cell degranulation was directly proportional to the number of adherent bacteria on the cell surface in the initial period of the interaction. Using a mouse model of bacterial peritonitis, we demonstrated mast cell degranulation and histamine release by type 1 fimbriated bacteria in vivo. Furthermore, beads coated with FimH but not with FimA, the major subunit of type 1 fimbriae, evoked mast cell release of histamine in vivo in amounts comparable to that elicited by type 1 fimbriated E. coli. These studies reveal that mast cells can be degranulated by interaction with type 1 fimbriated E. coli and that FimH, the mannose-binding component of the fimbriae, is a potent mast cell stimulant.