The outcome of TCR engagement with peptide-MHC is of central importance for the immune response of the host. TCR antagonism is one phenomenon known which is characterized by selective inhibition of T cell responses by non-stimulatory antigen analogs. T cell anergy is another state resulting in T cell unresponsiveness, generally characterized by lack of proliferation and lymphokine production. In the present study, the relationship between TCR antagonism and T cell anergy was examined by using protocols known to induce either phenomenon. Re-isolation experiments demonstrated that antagonized T cells were not tolerized, in that they were fully capable of responding to a subsequent antigen challenge. Conversely, while high doses of soluble antigen could efficiently induce T cell tolerance, TCR antagonists, either alone or in conjunction with suboptimal antigen doses, could not. Taken together, these data demonstrate that TCR antagonism and T cell tolerance are phenomena independent of each other.