In this study, the influence of surface morphology and wettability of both degradable and nondegradable polymer films on the inflammatory response after subcutaneous implantation in the rat was investigated. Degradable nonporous, porous, and combi (porous with a nonporous layer on one side) poly(L-lactic acid) (PLLA) films and nondegradable polytetrafluoroethylene (PTFE) and (porous) expanded PTFE (e-PTFE) were used. Contact angles measurements indicate that PLLA is more hydrophillic than PTFE. Assessment of the inflammatory response was performed after various periods of implantation (up till 180 days), with both conventional light microscopy and immunohistochemistry using monoclonal antibodies (mAbs). The inflammatory response observed initially can largely be considered as part of the wound healing reaction, and up till day 40 the inflammatory response against PLLA was minimally more intense than against PTFE (porous as well as nonporous). From day 40 on, the PLLA films provoke a more intense inflammatory response as compared to the PTFE films. Both porous PLLA and the porous side of the combi PLLA film provoke a more intense inflammatory response than nonporous PLLA and the nonporous side of the combi PLLA film, respectively. In general, PTFE and e-PTFE films provoke an inflammatory response which is minimally more intense than the one provoked by the sham operation. Almost no ingrowth of tissue was observed in the porous e-PTFE films. In contrast, there was abundant tissue ingrowth in and an inflammatory response against porous PLLA. It can be concluded that biodegradable PLLA films provoke a more intense inflammatory response than nondegradable PTFE films. Also, porosity enhances the inflammatory response. However, porosity enhances the inflammatory response only when the wettability of a biomaterial permits cellular ingrowth.