Stromal-derived factor-1 (SDF-1), the only known ligand for the chemokine receptor CXCR4, is broadly expressed in cells of both the immune and central nervous systems, and it can induce the migration of resting leukocytes and hemopoietic progenitors. SDF-1 mRNA was previously detected in human thymus-derived stromal cells, but its role in thymopoiesis was unknown. Here we show that SDF-1 is expressed in medullar epithelial cells forming Hassall's corpuscles (HC). In search of the cell type that may be attracted by SDF-1(+) cells in the medulla, we determined that dendritic cells (DC) could be found in situ in close proximity to SDF-1(+) epithelial cells in HC. In HIV-1-infected SCID-hu thymuses, DC contained apoptotic cells and were located within enlarged HC. It was further demonstrated that uptake of apoptotic thymocytes by immature DC induced an increase in CXCR4 expression and SDF-1-mediated chemotaxis. Our data suggest a role for SDF-1 in the elimination of apoptotic thymocytes.