The effect of the tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) on intravenously transplanted hematopoietic stem cell engraftment into the bone marrow (BM) of irradiated mice was studied. When 5 x 10(4) marrow cells were transplanted into lethally irradiated mice given 10 microg AcSDKP, the survival of these animals 4 weeks posttransplantation increased markedly from 20.0 +/- 4.4% to 86.1 +/- 4.8%, the same result as that obtained from mice transplanted with 5 x 10(5) cells without AcSDKP treatment. Increased numbers of hematopoietic stem cells, including spleen colony-forming unit and colony-forming unit granulocyte-macrophage, were observed in the BM of AcSDKP-treated mice 1 and 8 days after transplantation. This finding suggested that AcSDKP influenced homing of hematopoietic stem cells into the BM of lethally irradiated animals. This enhancing activity of AcSDKP was neutralized by the simultaneous administration of an anti-AcSDKP polyclonal antibody. Furthermore, recovery of leukocytes in peripheral blood occurred faster in AcSDKP-treated than in untreated transplanted mice. These findings may provide a basis for the clinical use of AcSDKP in BM transplantation patients.