The nonobese diabetic (NOD) mouse develops a high incidence of autoimmune diabetes and is believed to be a good model for insulin-dependent diabetes mellitus (IDDM) in humans. We isolated T-lymphocyte lines from islets of newly diabetic NOD mice, some of which are autoreactive to NOD spleen cells. Because autoreactive T-lymphocytes have been implicated in immune suppression, we injected NOD mice with an autoreactive T-lymphocyte line. The injected mice had a marked decrease in incidence of IDDM compared with control mice. Moreover, their islets showed no insulitis at 1 yr of age. We conclude that autoreactive T-lymphocytes can prevent the development of IDDM in NOD mice. This result suggests that 1) islets contain both effector cells capable of damaging pancreatic beta-cells and cells able to regulate this autoimmune response, and 2) development of IDDM depends on the balance between these opposing forces.