Lymphocyte migration patterns into and within lymphoid organs and nonlymphoid organs such as the skin as highly regulated and controlled by a variety of factors, some of which we are beginning to understand at a basic cellular and molecular level. In the case of lymphocyte migration into lymphoid organs, recirculatory patterns and preferences appear to be mediated by selective recognition via lymphocyte membrane receptors of distinctive determinants expressed by specialized endothelial cells in different organ sites. A similar model in which endothelial cells in the skin share common determinants with endothelial cells in peripheral lymph nodes can be developed to explain the migration patterns of lymphocytes from the blood into the skin. Cells that have undergone blast transformation in the microenvironment of the skin or peripheral lymph nodes, or both, appear to recirculate selectively within this particular sphere of immunologic influence, whereas other cells that undergo this transformation in the microenvironment of the gastrointestinal tract and its draining mesenteric lymph nodes selectively recirculate within that sphere of immunologic influence. This preferential recirculation increases the probability that the immunologic defense needs of a given region or tissue such as the skin will be met efficiently and appropriately. Finally, some of the phenotypic characteristics favoring the movement of lymphocytes from the bloodstream into the dermis (such as recent stimulation and the presence of T-cell surface markers) also seem to favor lymphocyte migration into or retention in the epidermis. However, under appropriate circumstances, epidermotropism can be exhibited by both major subsets of T cells as well as a variety of non-T cells.