Successful islet allografts can be established in rats bearing long surviving renal allografts, without additional immunosuppression, when kidney and islet donor animals are of the same strain. The applicability of such a scheme to clinical practice has been investigated in a large animal model of diabetes: the pancreatectomized dog. Eight dogs with previously established renal allografts and immunosuppressed with cyclosporin A received islet allografts from their respective original kidney donors. The median islet graft functional survival was only 10.5 days, significantly less than for six similarly immunosuppressed dogs receiving islet allografts alone (48.5 days, P less than 0.05). Three of the sequentially transplanted dogs had had no renal graft rejection episodes before islet transplantation, yet their islet grafts were all rejected within 19 days. In the pancreatectomized dog, prior donor specific renal transplantation has an adverse effect upon subsequent islet graft survival.