The integrin-associated protein (IAP) has been shown to function in a signaling complex with beta3 integrins, influencing the migration of phagocytic cells into inflamed tissues. We have previously shown that gene-targeted mice deficient for IAP succumbed to peritonitis when inoculated with gram-negative bacteria. The aim of this study was to assess the role of IAP in our recently established model of haematogenously induced Staphylococcus aureus septicaemia and arthritis. In this model, neutrophils play a crucial role in the early phase of the infection. Mice lacking IAP and congenic controls were intravenously inoculated with S. aureus LS-1. The IAP-/- mice were resistant to developing clinical signs of arthritis compared with their IAP-expressing littermates. The clinical findings were corroborated by histopathological evaluation indicating that the IAP-/- mice had less cartilage and bone destruction in the joints. We believe that a delayed migration of leukocytes into the joints of mice lacking IAP expression leads to decreased susceptibility to develop S. aureus-induced arthritis.