Bovine lactoferricin, a pepsin-generated antimicrobial peptide from bovine lactoferrin active against a wide range of bacteria, was tested far its ability to influence the adhesion and invasion of Yersinia enterocolitica and Yersinia pseudotuberculosis in HEp-2 cella. The addition of non-cytotoxic and non-bactericidal concentrations of lactoferricin to celi monolayers before infection, under different bacterial growth experimental conditions, was ineffective or resulted in about a 1O-fold increase in bacterial adhesion, whereas, in bacteria grown in conditions allowing maximal invgene expression, a 1O-fold inhibition of celi invasion by lactoferricin was observed. To confirm that the anti-invasive activity of lactoferricin was exerted against invasin-mediated bacterial entry, experiments were also performed utilizing Escherichia coli strain HB1 01 (pRI203), harbouring the inv gene from Y. pseudotuberculosis, which allows penetration of mammalian cells. Under these experimental conditions, lactoferricin was able to inhibit bacterial entry into epithelial cells, demonstrating that this peptide acts on inv-mediated Yersinia species invasion. As the inv gene produci is the mogi important virulence factor in enteropathogenic Yersinia, being responsible far bacterial adherence and penetration within epithelial cells of the intestina llumen and far the subsequent colonization of regional lymphnodes, these data provide additional information on the protective role of lactoferricin against bacterial infection.