Interleukin-2 receptor a chain (IL-2Ra) expression occurs at specific stages of early T and 6 lymphocyte development and is induced upon activation of mature lymphocytes. Young mice that lack IL-2Ra have phenotypically normal development of T and B cells. However, as adults, these mice develop massive enlargement of peripheral lymphoid organs associated with polyclonal T and B cell expansion, which, for T cells, is correlated with impaired activation-induced cell death in vivo. Older IL-2Ra-deficient mice also develop autoimmune disorders, including hemolytic anemia and inflammatory bowel disease. Thus, IL-2Ra is essential for regulation of both the size and content of the peripheral lymphoid compartment, probably by influencing the balance between clonal expansion and cell death following lymphocyte activation.