The effect of O,O‐dimethyl, S‐ethyl phosphorothioate (OO‐Me S‐Et) on macrophage function and the responses of T‐ and B‐cells of the immune system were investigated using an in vitro model. The role of glutathione (GSH) enhancement of OO‐Me S‐Et suppression of immune responses was studied after either direct culturing with spleen or B‐cells alone or coculture of B‐cells with either B‐ or T‐cells with or without preincubation with OO‐Me S‐Et and glutathione enriched cytosol. The results indicated that OO‐Me S‐Et, when preincubated with CSH, suppresses immune responses through an inhibition of B‐ and T‐cell functions. Both cytotoxic T‐lymphocyte (CTL) generation and antibody production were impaired. In mixing experiments of pre‐treated and normal cells, the inhibitory effect was also observed on macrophages and helper T‐cells responding to a T‐dependent antigen. It appears that the immunosup‐pressive effect of OO‐Me S‐Et is due to impairment of collaboration of T‐ and B‐cells, i.e., mainly due to impairment of T‐cell functions. The immunotoxic effect was only detectable when glutathione was present in the preincubation mixture.