The biomaterial ePTFE is widely used in the clinical environment for vascular replacement or bypass, as well as in the repair of tissue defects, especially those involving the abdominal wall. The objective of this study was to evaluate the healing response to ePTFE prostheses implanted into a circulatory interface and a tissue interface, each in a different animal species. For vascular implants, the Sprague-Dawley rat (n = 60) was used, while the New Zealand white rabbit (n = 20) was used in the tissue replacement model. In the former, a vascular microprosthesis measuring 5 mm in length and 1 mm in internal diameter, having a porosity of 30 microns, was implanted into the common iliac artery. In the rabbit, a 7 x 5-cm fragment of ePTFE (Soft-Tissue Patch) was implanted into a defect in anterior abdominal wall that involved all the tissue layers. In this case, the prosthesis was left touching the intestinal loops. The implants were studied between 14 and 90 days of postimplantation by means of light microscopy, scanning electron microscopy, and immunohistochemistry. The latter involved the use of anti-rat (MAC-341) and anti-rabbit (RAM-11) macrophage-specific monoclonal antibodies. The behavior of the ePTFE in the different interfaces (vascular and abdominal wall) was similar with respect to the following aspects: the prosthesis presented a process of encapsulation which was more intense on the outer surface; colonization of the implant was limited to the outermost two thirds, with minimal invasion of the middle portion; colonization was absent on the edges of the prosthesis; collagenization of the interstice of the mesh occurred late; the foreign body reaction taking place on the outer surface was similar in both interfaces, with formation of a barrier consisting of macrophages and giant cells that did not penetrate the prosthesis; and, finally, in neither of the two models was vascular colonization of the PTFE prosthesis observed; rather, the angiogenic process was limited to the periprosthetic zones. The integration of the implant made of ePTFE is similar despite the differences in interfaces and the use of different animal species. The macrophage response does not determine the success or failure of the implant.