We have made three observations that are important for our understanding of the dynamics of presentation of diabetogenic Ags in immunologically induced diabetes. First, the APC in the islets of Langerhans were found normally to contain diabetogenic peptides on their I-Ag7 molecules. This was found in freshly harvested islet cells from prediabetic NOD mice and, importantly, from NOD.SCID mice. Second, the presence of diabetogenic lymphocytes improved the presenting function of intra-islet APC. We interpret this to mean that lymphocytes can regulate intra-islet APC function before the development of diabetes. Finally, spleen APC can be found bearing diabetogenic Ag after acute injury to islets. These APC may be important in lymphocyte stimulation outside the environment of the pancreas.