Histophilus somni strain 2336 contains a large open reading frame of 12,285-bp length, ibpA, encoding the immunoglobulin binding protein (IbpA) which is associated with H. somni serum resistance. To elucidate other functions of the strain 2336 IbpA protein, an ibpA isogenic mutant, 2336.A1, was created by replacement of an 11.6-kb ibpA sequence with a kanamycin resistant gene cassette. Both the mutant strain 2336.A1 and the wild-type strain 2336 adhered at similar levels to bovine turbinate cells, bovine endometrial epithelial cells and bovine macrophage-like FBM-17 cells. However, a remarkable cytotoxic effect associated with disruption of actin filaments was observed in FBM-17 cells infected with strain 2336 but not with strain 2336.A1. Cytotoxicity was also noted with the wild type but not the mutant in assays with murine J774.1 macrophage cells and bovine primary monocytes. Inhibition of phagocytosis of microspheres was found in assays with murine J774.1 cells and bovine primary monocytes infected with strain 2336 but not with strain 2336.A1. These results indicate that H. somni IbpA protein inhibits phagocytic activity of macrophages and monocytes, probably by disruption of actin filament structure.