Transgenic mice expressing simian virus 40 T antigen under control of the insulin gene regulatory region vary in their response to this protein. Each lineage is characteristically either tolerant to T antigen, or not, in which case autoantibodies arise with high frequency, and lymphocytes infiltrate and disrupt the pancreatic islets. Both non-tolerance and the autoimmune response appear to result from delayed onset of T antigen expression during beta cell development.