In order to evaluate the biological response induced by true methyl and hydroxyl surfaces, alkane thiols were immobilized onto gold. Initial protein adsorption from human plasma was measured in vitro by ellipsometry-antibody techniques and in vivo surface-cell interactions were evaluated in rat subcutaneous tissues for time periods ranging between 1 and 28 days. Rat mononuclear cells were studied after culturing (24 h) on the surfaces. Plasma protein experiments revealed deposition of fibrinogen onto the pure gold and the methylated surface. The hydroxylated surface tended to release the surface-associated proteins tested for by antibodies. None of the in vivolin vitro models used showed differences between the hydroxyl and methyl surfaces for spontaneous or augmented cell hydrogen peroxide and interleukin-1 alpha secretions. However, the different surface chemistries markedly affected the distribution of the cells that were recruited to the interfaces (cells in the fluid space and surface-associated DNA content on the retrieved implants) at late and early time periods. The results indicate that different implant surface properties, such as chemical functionality and hydrophobicity, influence specific events in the inflammatory cell response, and ultimately the wound healing around implantable materials.