In this study, we investigated the homing and initiation of division of fluorescently labelled adult mouse bone marrow cells after their intravenous injection into lethally irradiated congenic mice. After 2 h, only 3% of the transplanted cells remained in the blood, and∼ 35% could be retrieved from the marrow, liver and spleen in approximately equal numbers. Subsequently, the proportion of injected cells found in blood, liver and spleen decreased further, but increased slightly (to∼ 17%) in the marrow. Homing of progenitors followed a similar pattern. At 22 h post transplant, almost half of the injected cells in the blood, liver and spleen had completed a first mitosis; although these did not include progenitors with in vitro clonogenic ability. at the same time,> 90% of the injected cells recovered from the marrow had not yet divided. Parallel studies with CD44−/− mice showed these to contain a numerically and functionally normal stem cell population whose homing and activation in either CD44+/+ or CD44−/− hosts appeared unaltered. These results indicate homing mechanisms that favor more stable retention of transplanted marrow cells in the marrow of the recipient, more rapid activation of some of those cells that home to other sites, and a lack of change in either of these responses when either the transplanted or the recipient cells do not express CD44. Bone Marrow Transplantation (2000) 26, 559–566.