Both cloned murine helper T lymphocytes (HTL) and cytolytic T lymphocytes (CTL) proliferated and secreted lymphokines when stimulated with immobilized anti-T cell receptor monoclonal antibody (anti-TCR mAb). However, although proliferation of CTL increased and reached plateau levels as concentrations of anti-TCR mAb were increased, the proliferation of HTL decreased with high concentrations of anti-TCR mAb. A reduction of IL 2-dependent proliferation by CTL was observed when IL 2 was added to cultures of CTL in the presence of high concentrations of anti-TCR mAb, whereas IL 2-independent proliferation appeared to be unaffected by these concentrations of anti-TCR mAb. Inhibition of IL 2-driven proliferation caused by high concentrations of immobilized anti-TCR mAb did not seem to be mediated by soluble factors. Cells continued to express cell surface receptors for IL 2 and transferrin after treatment with immobilized anti-TCR mAb. Inhibition of IL 2-driven proliferation by high concentrations of immobilized anti-TCR mAb may represent a mechanism for regulating the proliferation of T lymphocytes. This inhibitory mechanism is initiated by stimulation of the T cell receptor, in this case by immobilized anti-TCR mAb, and is independent of other cells and factors.