Long-term function of isolated porcine islets was investigated in diabetic nude mice. Seven of eight mice that received transplants of porcine islets remained normoglycemic for 1 year with progressive weight gain. Circulating porcine C-peptide was detected throughout the study period. Intravenous glucose tolerance tests showed a rapid glucose clearance rate. Together with our recent finding that porcine islets contained within an immunoexclusion device achieved glycemic control in a totally pancreatectomized dog, these results clearly demonstrate that isolated porcine islets are capable of functioning for prolonged periods in xenogeneic hosts and are suitable for long-term use in an immunoexclusion device in a discordant host.