The utilization of dual maintenance therapy with tacrolimus and sirolimus (the Edmonton protocol) has been widely adopted as standard immunosuppression for islet cell transplantation. This immunosuppression regimen has numerous toxicities including renal dysfunction, anemia, and recurrent aphthous ulcers. We present a case of a 63-yr-old Caucasian female who received an isolated islet transplant. Over the first six months post-transplant, the patient developed severe anemia, intractable aphthous ulcers, and renal dysfunction. Islet transplant function was excellent and the patient is insulin-independent since the end of the second month post-transplant. However, because of the above toxicities, a decision was made to change her immunosuppression regimen eight months post-transplant to low dose tacrolimus, mycophenolate mofetil, and a monthly maintenance infusion of daclizumab. Since then, her aphthous ulcers have disappeared, renal function has improved, and islet cell function remains stable.