The normal beta-cell is in essence a closed-loop system for insulin delivery. The successful transplantation of islets into diabetics should provide a means of maintaining normoglycemia in the recipients and determining whether this would prevent, arrest, or reverse the complications of diabetes. The accomplishments leading toward this idealized objective have shown that in the experimental animal, diabetes can be reversed by islet transplantation. Early microvascular complications of diabetes are reversed. Three pretreatment procedures have been developed that prevent rejection of islets transplanted between strains of animals without immunosuppression of the recipients, and two pretreatment procedures have been shown to prevent immune rejection of rat islets transplanted into diabetic mice without the use of immunosuppressive drugs. The critical problems remaining are the development of procedures for the mass isolation of islets that would be required for human transplantation, and if this is successful, determining whether the pretreatment regimens that prevent rejection in mice and rats will be applicable to man.