Objective: After an initially successful islet cell transplantation, a number of patients return to C-peptide-negativity and are therefore discontinued in immune suppressive therapy. Some were found to develop Graves' disease. Research design and methods: Immune suppressive therapy was stopped in 13 type 1 diabetic islet cell recipients who had received one course of antithymocyte globulin and maintenance doses of mycophenolate mofetil and a calcineurin inhibitor. None had a history of thyroid disease. Results: In 4 patients clinical Graves' hyperthyroidism was observed within 21 months after discontinuation, and 30 to 71 months after start of immune suppressive therapy. All four exhibited a pretransplant positivity for thyroid peroxidase (TPO)-autoantibodies while the nine others were TPO-negative pre- and posttransplantation. Conclusions: Type 1 diabetic recipients of islet cell grafts with pretransplant TPO-autoantibody positivity exhibit a high risk for developing Graves' hyperthyroidism after immune suppressive therapy is discontinued for a failing graft.