Bovine adrenal chromaffin (BAC) cells were encapsulated in polymer membranes and placed into the lumbar intrathecal (subarachnoid) space of sheep for up to 12 weeks in the absence of immunosuppression. Humoral and cellular immunological responses in the sheep were evaluated over this time course using the following assays: (1) serum-dependent cytotoxic antibody determinations, (2) flow cytometric sheep anti-bovine IgM and sheep antibovine IgG antibody analysis, (3) alterations in cellular immune markers, and (4) T cell responsiveness of the host using one-way mixed lymphocyte reactions. Complement-dependent cytotoxic antibody testing demonstrated that none of the sheep implanted with the encapsulated BAC cells were sensitized to antigens from transplanted cells in the device. There were no alterations of cellular immune markers in the blood of the transplanted sheep and no positive T cell responses were elicited by exposure of unprimed or primed in vivo host lymphocytes to unencapsulated BAC cells in vitro. Morphological analysis of the explanted devices demonstrated that all capsules contained viable cells and 20 of 21 devices released basal and nicotine-stimulated norepinephrine as determined by HPLC analysis. These observations suggest that an encapsulating membrane can provide an immunoisolatory barrier enabling successful xenogeneic transplantation.