Antibodies to interleukin-2 (IL-2) have been reported in the sera of patients under therapies involving this cytokine and in the sera of patients infected with human immunodeficiency virus (HIV). Our study proves that auto-antibodies to IL-2 are present also, at a lower titre, in healthy individuals. These antibodies were affinity purified and studied for their capability to interfere with the in vitro biological activity of IL-2. Data obtained show that human anti-IL-2 antibodies can interfere with lymphocyte proliferation both in the lymphokine activated killer (LAK) cell assay and in the mixed lymphocyte reaction (MLR). However, the kinetics of inhibition by anti-IL-2 antibodies differs from LAK cell assay to MLR as the former are always inhibited in a time-independent manner, and the latter only by adding antibodies at the outset of culture. The neutralizing activity observed in vitro suggests that such antibodies play a part in the elaborate cytokine network by which the immune system regulates the amplitude and duration of its response.