The effect of mitogen-induced nonspecific suppressor T cells (Ts)2 2 Abbreviations used: Ts, T suppressor cell; MHC, major histocompatibility complex; TRF, T-cell replacing factor; Con A, concanavalin A; SN, supernatant; TNP, trinitrophenyl; TNP-KLH, trinitrophenylkeyhole limpet hemocyanin; rIl-2, recombinant interleukin 2; SRBC, sheep red blood cells; PFC, plaque-forming cell; Mφ, macrophage. on T-helper-cell activity was investigated using isolated clones of murine T-helper cells as targets. TNP-self-reactive Thy-1+, Ly1+ T-cell clones were isolated after continuous culture of T cells derived from picryl chloride-sensitized mice and were characterized by their ability to proliferate in an antigen-specific and MHC-restricted manner. In addition, selected T-cell clones were found to produce both interleukin-2 (Il-2) and T-cell replacing factor (TRF), lymphokines characteristic of helper T cells. Concanavalin A (Con A)-induced Ts cells inhibited the antigen-specific proliferation of these helper-T-cell clones in a noncytotoxic manner even in the presence of exogenous Il-2. This implied that failure to proliferate was not merely due to an inability of these clones to produce Il-2. The kinetics of suppression also suggested that early T-cell activation signals were not affected. Furthermore, coculture experiments indicated that while proliferation could be severely inhibited, the actual secretion of lymphokines such as Il-2 and TRF by the T-helper clones was not. Our data suggest that nonspecific Ts modulation of proliferation versus helper factor production are under separate control in cloned T-cell populations, with lymphokine secretion remaining intact in the presence of Con A-induced Ts cells.