T cell precursors migrate from extrathymic hematopoietic tissues and dlfferentlate after encountering the thymic microenvironment. We asked whether human T cell precursors express the CD44(Pgp-l/gp90HR) class of homing receptors that have been implicated in the traffic of hematopoietic cells, such as lymphocyte entry to peripheral lymphold organs. Flow cytometry and immunoprecipitation studies demonstrate that CD7⁺34⁺, CD1-2-3-4-8- 14-16-20- cells in bone marrow and thymus, which have been shown to exhibit features of T cell precursors, bear CD44. Immunohlstologoical studies show that clusters of thymocytes in the subcapsular and the inner cortex and most medullary thymocytes are clearly CD44⁺, whereas the expression of CD44 is selectively downregulated in CD3- and CD3^low functionally incompetent cortical thymocytes. The expression of CD44 is not restricted to T cell precursors but also occurs in thymic stroma, which bear a different molecular species of CD44. CD44-specific antibodies exert stimulatory effects on T cell precursors, a process that is dependent on stromal cells. We postulate that CD44 might be an adhesion molecule for precursor homing to thymus and that it participates in cell-to-cell interactions within the thymic environment.