OBJECTIVE To induce islet allograft long-term survival through cotransplantation of islet cells with sertoli cells. METHODS Testicular sertoli cells were prepared by digestion with collagenase, trypsin and DNase, and were cultured for 48 hours. Collagenase digested and Ficoll purified donor (Wistar rat) islets were cotransplanted with allogeneic sertoli cells in the absence of systemic immunosuppression. Terminal deoxynucleotidyl transferase-mediated X-dUTP nick-end labeling (TUNEL) was used to label apoptosis of lymphocytes surrounding the islet graft. RESULTS Cotransplantation of islets and 1 x 10(7) sertoli cells reversed the diabetic state for more than 60 days in 100% (6/6) of the chemically diabetic Sprague Dawley rats. Grafts consisting of islets alone or islets plus 1 x 10(5) sertoli cells survived only for 5-6 days. Apoptosis of lymphocytes surrounding the islets was quite clear. CONCLUSIONS Cotransplantation of islets with FasL+ sertoli cells induces local immune privilege and allows long-term graft survival without systemic immunosuppression.