Cytotoxic Necrotizing Factor 1 (CNF1) is a protein toxin from Escherichia coli that induces the activation of Rho, Rac, and Cdc42 GTPases, all involved in actin reorganization. Rac plays a further role in oxidase function. In epithelial cells, CNF1 has been reported to induce a phagocytic-like behavior in terms of a ruffle-driven ingestion of large material. We herein show that CNF1-activated epithelial cells may exert additional cell responses typical of professional phagocytes following stimulation, i.e., an increase in oxygen consumption and the generation of superoxide anions, Such effects were triggered by the contact of latex beads with epithelial cells and were significantly augmented by CNF1-induced Rac activation. Altogether our data indicate that Rac, one of the targets of CNF1, plays a pivotal role in these phenomena, suggesting the involvement in epithelial cells of a Rac-dependent NBDPH-oxidase complex similar to that employed by professional phagocytes,