The ability of interferon gamma (IFN-gamma) to inhibit the proliferation of type 2 T helper cells (T(H)2), but not that of type 1 (T(H)1) cells, suggests that helper cell subsets might differ in their activation of the IFN-gamma signaling pathway. The IFN-gamma-inducible signal transducing factor (STF-IFN gamma) was activated in murine T(H)2 but not in T(H)1 cell clones, because in the latter the second chain of the IFN-gamma receptor (accessory factor 1 or IFN-gamma R beta) was absent. Thus, T(H)1 cells use receptor modification to prevent the activation of STF-IFN gamma and achieve an IFN-gamma-resistant state.