A minute population of cells representing the earliest lymphoid-restricted precursor cells in the adult mouse thymus has been isolated recently in our laboratory. This population expresses low levels of CD4, very high levels of CD44 and has a surface antigenic phenotype similar to that of bone marrow hemopoietic stem cells. To examine the role of CD44 on these cells, and to ascertain its ligand, we analysed the ability of the early thymic precursor cells to bind hyaluronate (HA) which functions as a cell adhesion molecule and a ligand for CD44. We also examined if anti-CD44 antibodies (clones IM7.8.1 and KM201) can block the thymic precursor activity. The majority of the thymic precursor cells did not show specific HA binding, indicating that HA is not the ligand for the CD44 molecules expressed on these precursor cells. HA and CD44 interactions are therefore unlikely to play a role in development of cells at this early intrathymic precursor stage. When the purified intrathymic precursor cells were incubated with anti-CD44 antibodies before intravenous transfer into recipients, very few progeny cells were detected in the thymus, although progeny were found in the spleen and lymph nodes. Coating the cells with other isotype-matched antibodies did not have this effect. However, when the same anti-CD44-coated cells were transferred directly into the recipient thymus, normal levels of progeny cells were detected in this organ. This suggests that the CD44 on the intrathymic precursor cells is a homing molecule, able to direct cells to the thymus but utilizing some ligand other than HA.