Staphylococcal enterotoxin A (SEA), the most common cause of food poisoning, is capable of stimulating human T lymphocyte proliferation at concentrations as low as 10(-13) to 10(-16) M. SEA also induces the lymphokines interleukin 2 (IL 2) and interferon gamma (IFN gamma) at similarly low concentrations. HPL cultures were stimulated with SEA in the presence of antibodies to IL2 to determine the possible role of this lymphokine in its potent mitogenic effects. Polyclonal and monoclonal antibodies to human IL 2 blocked SEA-induced mitogenesis. Treatment of cultures with higher concentrations of SEA overcame the anti-IL 2 blockage, corresponding to induction of higher concentrations of IL 2. Blockage of HPL mitogenesis by anti-IL 2 antibodies also resulted in inhibition of IFN gamma production, which is dependent on IL 2. Neutralizing monoclonal antibody to IFN gamma failed to block SEA-induced proliferation. The data indicate that the induction of IL 2, but not IFN gamma, is a requirement for SEA induced lymphocyte proliferation. SEA food poisoning and IL 2 therapy for cancer result in similar toxic symptoms, characterized by malaise, fever, nausea or vomiting, and diarrhea. The similarity between SEA and IL2 toxic effects, the fact that SEA is a potent inducer of lymphokines such as IL 2, and the fact that IL 2 induction is a prerequisite for the mitogenic effects of SEA raises the intriguing question of the role of lymphokines such as IL 2 in SEA-induced food poisoning.