Several reports have suggested that encapsulation of orthopaedic and dental implants with fibrous tissue can lead to implant failure. The binding of cells to the surface of the implants is specific to amino-acid sequences, typically RGD. The specific objective of this study was to investigate the interaction of cultured human peripheral macrophages with specific amino-acid sequences to determine if adherence is due to the specificity of such sequence. Macrophages were seeded at a density of 1 x 10(5) cells on ultra high molecular weight polyethylene (UHMWPE) coated with either amino-acid heteropolymers of RGE, RGD, or amino-acid homopolymer Poly-L-Lysine. Cells were observed daily and morphology was recorded. The results showed that cells growing in the presence of 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. Cells growing on UHMWPE coated with RGE appeared irregularly (elongated and spindle) shaped and unevenly spaced. The cells growing in the presence of Poly-L-Lysine 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 UHMWPE coated with Poly-L-lysine showed a two-fold increase in activity over control and peptide treated groups. Immunochemical analysis for cytokine (IL-1) release as a measure of cellular reactivity revealed an increase level in the experimental groups after 24 hours and remained measurable over the duration of the experiment. Cells incubated on uncoated polyethylene showed no evidence of increased cytokine response. Overall, the results show macrophages can interact with specific coating on the material surface, and these surfaces can affect the adhesion process adherence. Use of RGE, which inhibits binding of the cells, may be a factor that can be used to coat implants to increase their longevity.