The migration of antigen-specific T cells to nonlymphoid tissues is thought to be important for the elimination of foreign antigens from the body. Here, we review the evidence that naive CD4(+) T cells are first activated by antigen presentation in secondary lymphoid organs, proliferate, and differentiate into effector cells capable of producing antimicrobial lymphokines. These effector cells then leave the secondary lymphoid organs and use newly acquired trafficking receptors to extravasate at sites of inflammation. We argue that antigen presentation is required to retain effector CD4(+) T cells in inflamed sites, and speculate on the antigen-presenting cells and adhesion pathways that are involved.