ABSTRACT. Lactoferrin and its derived N-terminal peptide may be important host defenses against Giardia lamblia. We showed earlier that lactoferrin and the derived peptides have potent giardicidal activity in vitro. Using indirect immunofluorescence, we now demonstrate binding of lactoferrin and the peptides to the live trophozoite surface. Iron strongly inhibited binding of lactoferrin, and decreased binding of the peptides, while certain divalent metal ions decreased binding of all forms by about half. Lactoferrin and the peptedes caused striking and complex morphologic changes in the trophozoite plasmalemma, endomembranes and cytoskeleton, and increases the electron density of the lysosome-like peripheral vacuoles.