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The phenomenon of stress cracking of pre-stressed Pellethane 80A was investigated by subjecting the polymer specimens to in vivo environments with different inflammatory reactions. It was found that in vivo cracking of stressed Pellethane 80A was related to cell/polymer interactions. A normal cellular response to the stressed implant could result in chemical degradation as well as cracking and rupture. On the other hand, the stressed (strained) polymer could be protected from deterioration, when the viable cell/polymer interactions were destroyed by a cytotoxic agent or suppressed by an anti-inflammatory drug. The cell/polymer interactions related to the biostability of polymer implants were further studied by correlating the location of foreign-body giant cells (FBGCs) with the cracked or pitted areas on the polymer surfaces. A technique combining scanning electron microscopy and a cell removal procedure was utilized. The results showed that the subcutaneous implantation of the polyetherurethanes produced a foreign body reaction accompanied by FBGC formation.