Beta cell destruction in autoimmune diabetes is accompanied by the presence of autoantibodies and autoreactive T cells against beta cell antigens. Autoantibodies to insulin are predictive of future diabetes in man and in the non-obese diabetic mouse model. Furthermore, the detection of peripheral autoreactive CD8(+) T cells in this mouse model is indicative of beta cell killing and correlates with the development of diabetes. We describe two protocols that are helpful for the detection of beta-cell autoimmunity in mice. The first protocol describes the detection of insulin-specific autoantibodies using a radio-binding assay. The other is a general CD8(+) T cell ELISpot protocol for the detection of peptide-specific responses of CD8(+) T cells from secondary lymphoid organs or pancreatic islets.