In addition to playing a major role in physiological immune responses against foreign antigens, the interleukin 2 (IL-2)-IL-2 receptor (IL-2R) system may also be implicated in autoimmune phenomena. Initial studies on the role of IL-2 in autoimmunity indicate a deficiency in the production of this lymphokine in autoimmune disease. Here, Guido Kroemer and Georg Wick review recent data supporting the notion that an excess of endogenous or exogenous IL-2 may aggravate autoaggression by triggering autoreactive effector cells, and they speculate that IL-2 might favor the de novo development of autoimmunity by breaking autotolerance.