To study surface property-dependent human monocyte adhesion and cytokine (IL-1 beta, IL-6, TNF-alpha) production, poly(tetrafluoroethylene/hexafluoropropylene) (FEP) polymer was modified to exhibit neutral, anionic, or cationic properties by incorporating amide (CONH2) and/or carboxyl (COOH) or aminoethyl amide [CONH(CH2CH2NH)nCH2CH2NH2] groups on the surface. Monocyte adhesion on surface-modified FEP polymers and cytokines released by monocytes/macrophages (MC/MO) into the culture medium were compared to control tissue culture polystyrene (TCPS) at days 1 and 8. On day 1, the neutral surface FEP polymer with incorporated amide (NH2) groups showed the greatest inhibition of adhesion, 89% (P < .01), and cytokine production (IL-1 beta with 58%, IL-6 with 70%, and TNF-alpha with 39%) compared to control TCPS. In contrast, the highly cationic [CONH(CH2CH2NH)nCH2CH2NH2] surface did not show significant (P > .01) inhibition of monocyte adhesion and cytokine production. When fibrinogen or IgG was preadsorbed to the surface, the inhibitory effects of the neutral surface FEP polymer on monocyte adhesion and cytokine production were not altered. In addition, other surface-modified FEP polymers showed similar inhibition of monocyte adhesion and cytokine production compared to TCPS. Specifically, as the incorporation of carboxyl (COOH) group content increased on FEP polymer surfaces, monocyte adhesion and cytokine production were also increased on day 1 with IgG preadsorption. On day 8, all surface-modified FEP polymers showed significant (P < .01) inhibition of monocyte adhesion when fibrinogen or IgG was preadsorbed. However, without protein (fibrinogen or IgG) preadsorption, monocyte adhesion was not significantly inhibited compared to control TCPS. In addition, cytokine production detected by ELISAs on day 8 showed no detectable levels of IL-1 beta and significantly decreased levels of IL-6 compared to day 1 for all tested polymers, with or without protein preadsorption. Interestingly, the level of TNF-alpha production on day 8 remained high although not as high as on day 1. Based on these results, we suggest that FEP polymers with neutral hydrophilic surface properties may adhere and activate the least number of monocytes, which are important mediators of biocompatibility.