Exposure of mice transgenic for a TCR (F5) to cognate peptide antigen results in thymic depletion of CD4+CD8+ cells and expansion and activation of peripheral CD8+ TCR(tg)+ T cells. In the thymus apoptotic DNA ladder is evident as early as 3 h after peptide injection. Long exposure of intact or thymectomized F5 TCR transgenic mice to peptide antigen leads to depletion of most of the peripheral CD8+ T cells bearing the F5 receptor, with the remaining cells having lower levels of transgenic TCR compared with non-treated animals. In the thymus of intact F5 TCR transgenic mice such continuous exposure to antigen results in the reappearance of CD4+CD8+ with lower levels of the transgenic receptor.