Cell surface adhesion receptors interact with a family of adhesion molecules known as integrins. It is assumed that the cells recognize and bind a specific amino acid sequence. It is likely that the host inflammatory response may be mediated via the recognition of the inflammatory cells with the specific integrin molecules. The mechanism of such behavior has not been fully elucidated. This investigation was designed to provide more insight regarding the cellular response associated with incubation of macrophages with polymers either freely in solution or adhered to surfaces. Peripheral macrophages were seeded at a density of 4 x 10(6) cells on supports coated with either amino-acid heteropolymers of RGE, RGD, or amino-acid homopolymer Poly-L-lysine. Cells were also seeded at the same density in 24 well plates and the wells were treated with RGD, RGE or Poly-L-lysine. The cells were examined morphologically and biochemically at 24, 48, and 72 hours. The results showed cells growing on supports coated with RGD had significantly (p < 0.05) higher numbers of cells adhering and remaining viable, in comparison to cells growing on Poly-L-lysine or RGE supports. Cells growing on supports coated with RGE appeared irregularly (elongated and spindle) shaped and unevenly spaced. The cells growing on Poly-L-Lysine coated supports showed cellular disruption and lysis, whereas cells growing on the RGD appeared intact, regularly spaced and began fusing into giant cells. Lactate dehydrogenase activity was used as a measure of membrane integrity, and cells grown on coated supports with Poly-L lysine showed a two-fold increase in activity over control and peptide treated groups. On the other hand, cells growing in media containing the free RGE, RGD and Poly-L-lysine showed no statistical differences in cell number, and did not show increased activity of LDH for the entire duration of the experiment. The data suggests that the RGD, RGE and Poly-L-lysine dissolved in solution are highly biocompatible to the macrophages. However, when they are attached to a support they can affect cellular adherence as well as cellular activation.