Integrins are transmembrane proteins that mediate attachment to extracellular matrix (ECM) proteins. Integrins act as ECM receptors and are believed to play a role in signal transduction and gene regulation, potentially influencing several cellular functions, including differentiation, growth, and migration. Several integrins have previously been found in bone cells in vivo and in vitro. Because the biologic fixation of orthopedic implants depends on optimal cell interactions at the interface, we examined whether integrins are involved in the attachment of osteoblasts to implant materials. In this study, we have used immunohistochemistry to examine the expression of integrins in primary human osteoblasts cultured on tissue culture polystyrene (PS), and rough and polished disks of the orthopedic alloys titanium-aluminum-vanadium (Ti) and cobalt-chrome-molybdenum (CC). The integrin subunits, alpha 2, alpha 3, alpha 4, alpha 5, alpha v, alpha 6, beta 1 and beta 3, were expressed by primary human osteoblasts cultured on PS coated with various ECM molecules. However, alpha 5 and alpha 6 were notably absent in cells attached to the alloys. Also, alpha 3 was not present on rough Ti, polished CC, or rough CC, and beta 3 was not expressed by cells on rough CC. Thus, the nature of the metal alloy appeared to influence the expression of particular integrins. As a result, the ability of cells to adhere to and receive messages from the extracellular matrix may also be influenced by the substratum. These differences may explain previously observed differences in degree of cell attachment to these metals.