The effect of silicone biomaterials on the immune system still remains largely unknown. This study was undertaken to determine the extent to which silicone elastomer, with or without either pre-adsorbed human serum albumin (HSA), IgG, fibrinogen or whole plasma, can activate peripheral blood monocytes. Monocytes were isolated from buffy coats from the local Red Cross Blood Center. Monocytes were cultured for 18h, culture supernatant collected, and analyzed for IL-1β, IL-6 and TNF-α by employing commercial ELISA kits. Monocytes, in contact with either polystyrene or silicones without protein adsorption, were minimally activated as evidenced by the low concentration of all the cytokines measured. On the other hand, monocytes became activated when in contact with silicones having adsorbed either of the above proteins. The silicone gel, silicone oil and silicone gel/oil combination appeared to cause the monocytes to secrete nearly twice the amount of all three cytokines as compared with silicone elastomer. This result may be a function of the increased effective surface area produced by the silicone gels and silicone oils. Contact angle measurements confirm that silicones have a very hydrophobic surface, whereas tissue culture grade polystyrene (TPST) is hydrophilic. We know that hydrophobic surfaces tend to be much more denaturing to adsorbed proteins than hydrophilic surfaces. Thus our results indicate that plasma proteins adsorbed to very hydrophobic surfaces cause monocytes to secrete significant amounts of IL-1β, IL-6 and TNF-α.