T-cell anergy is a state of immunological tolerance characterized by unresponsiveness to antigenic stimulation. Previous studies have shown that anergy is induced in T cells following stimulation in the absence of adequate costimulatory signals. These cells fail to respond to stimulation via the T-cell receptor (TCR), and fail to produce normal levels of interleukin-2 (IL-2). We present results here which show that low concentrations of the superantigen staphylococcal enterotoxin A (SEA) in the absence of antigen-presenting cells induced both proliferation and anergy in the A.E7 T-cell clone. Furthermore, under these conditions, the A.E7 clone remained responsive to exogenous IL-2. Fluorescence-activated cellular cytometry analysis revealed unaltered expression of the TCR/CD3 complex in the anergized clone; however, both CD4 and CD25 expression increased after 24 hr of stimulation by SEA under these conditions. Interestingly, a low level of IL-2 production was measured during the induction of anergy. Most strikingly, stimulation of the A.E7 clone by SEA in combination with exogenous IL-2 resulted in a more pronounced state of anergy. These results suggest that the induction of anergy is a process that is essentially independent of the production of IL-2.