It has been proposed that the development of insulin-dependent diabetes is controlled by the T helper 1 (T_H1) versus T_H2 phenotype of autoreactive T_H cells: T_H1 cells would promote diabetes, whereas T_H2 cells would actually protect from disease. This proposition was tested by establishing cultures of TH1 and TH2 cells that express an identical diabetogenic T cell receptor and comparing their ability to initiate disease in neonatal nonobese diabetic mice. T_H1-like cells actively promoted diabetes; T_H2-like cells invaded the islets but did not provoke disease—neither did they provide substantial protection.