Islet transplantation has been investigated as a treatment for Type 1 diabetes mellitus in selected patients with inadequate glucose control despite insulin therapy. However, the perennial hope that such an approach would result in long-term freedom from the need for exogenous insulin, with stabilization of the secondary complications of diabetes, has failed to materialize in practice. The goal of the present study is therefore to improve the safety and efficacy of clinical islet-alone transplantation by minimizing dependence on calcineurin-inhibitor therapy - thereby avoiding potential nephrotoxicity, and furthermore improving success with single-donor islet infusions by avoiding all diabetogenic immunosuppression. Campath-1H, combined with Infliximab induction therapy provides a unique opportunity to minimize dosing of maintenance long-term immunosuppression while further promoting islet engraftment.