Enteropathogenic Escherichia coli (EPEC) may be considered a paradigm for a multistage interaction between pathogen and host cell. EPEC strains produce a type IV pilus that is associated with initial adherence to host cells, and these strains possess a type III secretion apparatus that is necessary for transducing signals to host cells. Secretion of three Esp proteins is required for activation of a phosphotyrosine-containing receptor that allows EPEC to bind intimately to host cells via the bacterial outer membrane protein intimin. Intimately attached bacteria rest upon a pedestal composed of host cytoskeletal proteins in an arrangement recognized as the attaching and effacing phenotype. The precise molecular interactions that lead to these dramatic alterations in the host cell cytoskeleton remain to be elucidated.