The T-cell repertoire is formed during T lymphocyte maturation in the thymus. There is, however, increasing evidence that there are additions to, and modifications of, this repertoire by extrathymic events. Most importantly, mature peripheral T cells are not only susceptible to activation signals but also to tolerance induction upon encounter of extrathymic antigen. An understanding of these inactivation processes should result in strategies for specific immunosuppression in organ transplantation and autoimmune diseases.