We have previously shown that the engagement of CD4 by specific antibody in the mouse initiates a T cell apoptosis response with the following features: spleen and lymph node CD4+ T cells migrate into the bloodstream within minutes of anti-CD4 administration where they exhibit the phenotype of null cells. If they are capable of expressing functional Fas protein on their surface they degrade their DNA and disintegrate rapidly. We show here that the engagement of the T cell antigen receptor blocks the CD4-mediated deletion process in mouse. Anti-CD4-reactive T cells avoid the exodus into the bloodstream when their TCR is engaged by anti-CD3 or by a superantigen, do not modulate surface receptors and are not deleted. In contrast to the apoptosis-inducing CD4-specific antibody which causes migration of lymphocytes from lymphoid organs into the blood stream, the T cell-activating CD3-specific antibody causes lymphoid cell redistribution in the opposite direction, from the bloodstream to lymphoid organs. The TCR-mediated protection of T cells against CD4-mediated deletion lasts for several hours but ceases before the T cells become blasts.