Neonatal thymectomy (Tx) of mice at day 3 after birth (Tx‐3), but not day 7 (Tx‐7), induces organ‐localized autoimmune diseases such as oophoritis and gastritis. Lesions in Tx‐3 mice can be prevented by injection of splenic CD4⁺ cells from syngeneic normal mice, and this CD4⁺ population with suppressor activity is activated extrathymically by self antigens. Since it is speculated that these CD4⁺ T suppressor cells (Ts) express the interleukin‐2 receptor (IL‐2R) as an activated T cell population, an attempt was made to eliminate these Ts from the developing immune system of Tx‐7 mice and normal mice by i.p. injection of anti‐IL‐2Rα monoclonal antibodies. Interestingly, organ‐localized autoimmune disease with quite similar characteristics to those observed after neonatal Tx developed in not only Tx‐7 mice, but also normal mice. The results thus indicate that CD4⁺ cells expressing IL‐2Rα play an important role, as Ts in the periphery, in maintaining immune tolerance.