Recent studies have demonstrated that antigen analogs can act as powerful and specific inhibitors of T cell activation. Analysis of various experimental systems suggests that this effect might be related to engagement of the T cell receptor (TCR) by low-affinity ligands and that the observed inhibition may be mediated by interference with membrane events crucial for signal transduction, such as proper TCR oligomerization. In addition, experimental data obtained by our laboratory and others suggest that TCR antagonism may be of significant value as a therapeutic approach and as a tool to dissect the process of thymic education.