A cDNA coding for δ-giardin was cloned from Giardia lamblia trophozoites to localize the protein and to study its function in mediating surface attachment. Recombinant δ-giardin antigen was expressed in Escherichia coli as a poly-histidine fusion protein and was purified by affinity chromatography for production of antisera to δ-giardin. By immunoblotting analysis, antisera to recombinant δ-giardin antigen recognized a 31-kDa protein on G. lamblia trophozoites. Anti-recombinant δ-giardin was used to localize the native protein to the trophozoite ventral disk in both immunofluorescence and immunoelectron microscopy assays. Pre-treatment of G. lamblia trophozoites with anti-δ-giardin sera caused morphological changes in the parasite and inhibited trophozoite binding to the surface of cell culture slides. Binding of antibodies to δ-giardin may provide a means of inhibiting attachment of G. lamblia trophozoites to the intestinal epithelium and thereby prevent clinical giardiasis.