Long-surviving Lewis (RT-1(1)) renal allografts (LS-LEW) were induced in 20 DA (RT-1a) rats by 14-day treatment with cyclosporine . All were made diabetic 100 days after transplantation using streptozotocin; 7 LS-LEW were untreated and all remained diabetic; 5 LS-LEW were given Lewis islets beneath the kidney capsule without further immunosuppression. Prolonged graft survival (greater than 100 days) was seen in 4 rats. Lewis islets were given into the portal vein in 5 LS-LEW. Prolonged graft survival was seen in 4 rats. Third-party BN islets were given beneath the kidney capsule in 3 LS-LEW; these islets were rejected in less than 9 days. In contrast Lewis islets transplanted into untreated diabetic DA rats beneath the renal capsule or into the portal vein survived for a mean of 8.3 days and 4 days, respectively. In a separate experiment long-surviving Lewis renal allografts were induced in 7 PVG rats (LS-PVG) by cyclosporine treatment. These animals were made diabetic 100 days after transplantation and then were given Lewis islets under the renal capsule of the transplant kidney. Prolonged islet graft survival was seen in 6 rats, and 5 diabetic PVG rats given Lewis islets beneath the renal capsule rejected the islets within 8 days. Thus, once a recipient rat has accepted a renal allograft under the influence of cyclosporine treatment, it will accept permanently an islet allograft of the same strain as the kidney. This effect applies to both strain combinations tested, is not influenced by the site of islet implantation, and is specific for islets of the same strain as the renal allograft.