Well-characterized aliquots of adult porcine and rat islets of comparable β-cell mass were transplanted under the kidney capsule of streptozotocin-induced diabetic nude mice. In both porcine and rat islet grafts, β-cell mass decreased significantly in the first 2 months and stabilized thereafter. As with β-cell mass, insulin content decreased significantly in the first 2 months to almost 40% of that originally implanted. In porcine grafts, however, insulin content at 4 months was significantly higher than at 2 months. The endocrine non-β-cell mass of grafts also decreased significantly after transplantation: in porcine grafts, the decrease was less than in rat and was limited to the first 2 months. β-cell replication of engrafted islets was significantly lower in porcine than in rat grafts. Although β-cell mass of porcine and rat grafts was similar at all time periods, recipients of porcine islets required a significantly longer time to reach normal glucose levels; nonetheless, their blood glucose levels continued to decrease and stabilized at levels significantly lower than those of normal mice. During oral and intraperitoneal glucose tolerance tests, blood glucose increased only slightly in both the recipients of porcine and rat grafts. When graft-bearing kidneys were perfused in situ, porcine islet grafts showed a 20-fold increase in insulin release in response to both glucose and arginine. In conclusion, this evidence that adult porcine islet grafts can bring glucose levels to those that are normal for humans provides further support of their potential for human islet replacement therapy.