Recent updates of the Edmonton trial have shown that insulin independence is progressively lost in approximately 90% of islet transplant recipients over the first 5 years. Early prediction of islet graft injury could prompt the implementation of strategies attempting to salvage the transplanted islets. We hypothesize that islet damage is associated with the release and detection of insulin mRNA in the circulating blood. Whole blood samples were prospectively taken from 19 patients with type 1 diabetes receiving 31 islet transplants, immediately prior to transplantation and at regular time-points thereafter. After RNA extraction, levels of insulin mRNA were determined by quantitative reverse tran-scriptase-polymerase chain reaction. All patients exhibited a primary peak of insulin mRNA immediately after transplantation, without correlation of duration and amplitude with graft size or outcome. Twenty-five subsequent peaks were observed during the follow-up of 17 transplantations. Fourteen secondary peaks (56%) were closely followed by events related to islet graft function. Duration and amplitude of peaks were higher when they heralded occurrence of an adverse event. Peaks of insulin mRNA can be detected and are often associated with alterations of islet graft function. These data suggest that insulin mRNA detection in the peripheral blood is a promising method for the prediction of islet graft damage.