To address trafficking of transplanted marrow cells immediately after intravenous infusion, we examined the early fate of infused non‐adherent, low‐density donor bone marrow cells in a syngeneic mouse model. The presence of infused donor cells, marked with indium‐111 oxine (¹¹¹In), with the fluorescent dye PKH26, or by a detectable transgene marker, was evaluated at 3–48 h in a variety of tissues, including peripheral blood. All three cell‐marking methods indicated a rapid (< 4 h) influx of cells into the bone marrow, liver, spleen, muscle and other tissues. Moreover, these tissues remained positive for the 48 h observation period. Interestingly, analysis of PKH26‐positive cells in non‐myeloablated animals demonstrated that approximately 17% of infused donor marrow cells localized to the marrow space within 15 h, whereas a smaller proportion of donor cells (~ 1–2%) localized to the marrow in recipients preconditioned by irradiation. In an effort to enrich for cells that specifically home to the bone marrow, PKH26‐labelled donor marrow cells were recovered from the first host and infused into a secondary recipient. Although this was a phenotypically undefined population of cells, no increase was observed in the relative fraction of PKH26‐labelled cells returning or ‘homing’ to the marrow of the second recipient. Taken together, these data suggest both that marrow engraftment may be mediated by non‐specific ‘seeding’ rather than a specific homing signal, and that efficient targeting of transplanted cells to the marrow is a complex multifaceted process.