Developing T cells which recognize self-proteins are specifically deleted by the process of negative selection in the thymus. This review summarizes data from both in-vitro and in-vivo systems on the cellular and biochemical requirements that play roles in this process. We first consider the involvement of co-receptors and antigen presenting cells in negative selection. Next, we discuss the involvement of various signalling pathways in thymocyte deletion, particularly under conditions of limiting stimulation. Finally, these data are discussed in terms of how positive and negative selection are regulated during T-cell development.