The biocompatibility of radiofrequency plasma polymerized films (less than 100 nm thick) deposited on biomedical polymer supports has been characterized by in vitro and in vivo methods. The polymer interface materials covered a wide range of elemental composition and surface properties, and were prepared from N-vinyl-2-pyrrolidone, gamma-butyrolactone, n-hexane, and hexamethyldisilazane (PPHMDSZ). The biocompatibility studies showed that the interface materials were noncytotoxic to mouse and human fibroblasts, as shown by morphologic evaluation, and by determination of extracellular LDH; and they did not stimulate interleukin-1-like production from human monocytes, as indicated by a thymocyte proliferation assay. The human fibroblast proliferation assay showed that three of the polymers supported cell growth at levels comparable to, or greater than, polymer controls, while the hydrophobic PPHMDSZ inhibited both cell attachment and proliferation. The response to subcutaneous implantation for all test materials was indicative of biocompatibility, with rapid resolution of the acute phase response and normal wound healing. The wide range of composition and surface properties for the plasma polymerized films evaluated in this study suggest that this general class of materials is likely to exhibit excellent biocompatibility.