Human mononuclear cells stimulated with staphylococcal enterotoxin A (SEA) for 2–6 days significantly suppress [3H]thymidine incorporation and reduce the levels of interleukin 2 (IL‐2) and interferon (IFN) in culture medium when added to fresh, polyclonally activated mono‐nuclear cells. The inhibitory capacity of the cells correlates well with the expression of IL‐2 receptors. Lymphocytes obtained 3 days after stimulation with SEA, when the IL‐2 receptor expression is high, are more potent inhibitors than cells obtained 2, 6, 11 or 14 days after stimulation, when the IL‐2 receptors are less expressed on lymphoeytes. T4′ T8′ cells were both found to be inhibitory. Irradiation of the cells with 15 Gy before stimulation with SEA reduced but did not climinate their suppressive capcity. The expression of the IL‐2 receptor was lower in the irradiated cells. Irradiation or mitomycin‐C treatment of cells after 3 and 5 days of SEA exposure had no effect on their inhibitory capacities. Pretreatment of the cells with IL‐2 could partially reverse their suppressive effect on recorded IL‐2 levels of stimulated fresh cultures. A complete reversal was obtained with the anti‐Tae monoclonal antibody, which binds to the IL‐2 receptor. The collective data show that the SEA‐included suppression of IL‐2 activity in lymphocyte culture medium is not due to a suppression of the IL‐2 production but rather depends on depletion of IL‐2 due to absorpt