To study the basis for immunological tolerance of peripheral tissue‐specific antigens, a transgenic mouse line was established that expresses the influenza hemagglutinin (HA) on pancreatic islet β cells (Ins‐HA transgenic mice). When followed up to 14 months of age, Ins‐HA transgenic mice did not develop spontaneous autoimmune disease. Upon immunization with HA‐expressing viruses, high titers of HA‐specific circulating antibody were detected; however, T cell responses by both the T helper and T cytolytic compartment were markedly reduced as compared with transgene‐negative littermates, and no evidence could be found for islet infiltrates. Adoptive transfer of histocompatible lymphocytes from transgene‐negative mice plus virus into irradiated Ins‐HA hosts resulted in islet inflammation dominated by CD4⁺ T cells, indicating that the HA antigen was accessible to activated T cells. These results suggest that T cells can be rendered tolerant of antigens expressed outside the thymus.