Bile salts are prevalent in the mammalian intestine, a natural habitat of Escherichia coli. The bile salts deoxycholate, chenodeoxycholate, ursodeoxycholate, and glycocholate were tested for their effect on induction of 13 specific stress response genes. The most consistently activated E. call promoters were those for genes micF, osmY, and dinD. MicF and osmY gene products are associated with membrane functions and are responsive to oxidative stress. DinD is induced by DNA damage as part of the SOS response. These results indicate that bile acids, to which E. call are naturally exposed, induce expression of specific stress response genes, possibly in response to membrane perturbation, oxidative stress, and DNA damage. Altered expression of stress-response genes may also promote interaction of E. coli with cells of the colonic epithelium.