Leukotactin-1 (Lkn-1) is a human CC chemokine that induces chemotaxis of neutrophils, monocytes, eosinophils, and lymphocytes and suppresses colony formation of myeloid progenitor cells in vitro. Present studies evaluated the myeloprotective capabilities of Lkn-1 in vivo against Ara-C and 5-fluorouracil (5-FU). The effect of Lkn-1 on myelopoiesis was first assessed in vivo by injecting recombinant Lkn-1 in C3H/HeJ mice. Lkn-1 rapidly decreased cycling rates and absolute numbers of myeloid progenitor cells in marrow. Lkn-1 administration prior to and during the chemotherapeutics treatment resulted in increased progenitors for colony-forming units-granulocyte/macrophage (CFU-GM), colony-forming units-granulocyte/erythroid/megakaryocyte/macrophage (CFU-GEMM), and burst-forming units-erythroid (BFU-E) compared with a saline-treated group. The protective effects lasted until day 3 after the termination of Ara-C administration and until day 7 after the termination of 5-FU administration. The results indicate that Lkn-1 protects bone marrow myeloid progenitor cells when cytotoxic chemotherapeutics are used in a preclinical setting. These results may be of use in clinical treatment for myeloprotection.