Intrasplenic autotransplantation of islet fragments prepared by ductal perfusion constitutes a reproducible system for islet delivery to apancreatic dogs. The animals are normoglycemic from the time of grafting, and graft failure is rare. In this study, apancreatic dogs received islet autografts (controls), autografts plus oral cyclosporine, and allografts plus oral cyclosporine. Therapeutic blood levels of cyclosporine were documented by radioimmunoassay. However, allografts and autografts ceased to function after initial normoglycemia in all animals that received cyclosporine, and four out of six autografts failed. Normoglycemia persisted in the control-autografted animals for the duration of the study. Microscopic sections of the failed grafts demonstrated meager tissue survival but no evidence of rejection by cellular infiltration.