Little is known about the fate of autoreactive CD4 T cells in blood. Using a mouse model for spontaneous autoimmune diabetes we demonstrated that the status of the autoimmune process in pancreas could be pictured through the frequency and phenotype of autoreactive CD4 T cells in the blood. Early during the prediabetic stage, the frequency of these cells in blood decreased as a consequence of their recruitment in the pancreas. This was followed by an imbalance between CD4(+)CD25(+) and CD4(+)CD69(+) T cells in the pancreas that was mirrored in the phenotype of autoreactive T cells in the blood. Waves of activated CD4(+)CD69(+) T cells in blood preceded the disease onset suggesting that the autoimmune attack on pancreas is a discontinuous "hit-and-run" rather than a continuous process. Tracking autoreactive CD4 T cells in blood may help in identifying prediabetic humans and monitoring the disease progression during therapeutic interventions.