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To establish a human monocytic leukemia model with central nervous system infiltration in BALB/c nude mice.BALB/c nu/nu mice, pretreated by splenectomy, cytoxan intraperitoneal injection, and sublethal irradiation, were transplanted intravenously with human monocytic leukemic cell line SHI-1. The leukemic cells engrafted in the mice were traced by RT-PCR, histopathological examination, immunohistochemistry and FCM.After engraftment of SHI-1 cells in SCI-nu/nu mice, multiple organs were involved and green solid neoplasms were formed in some organs. Paralysis was developed in some mice at both of the rear legs. Histopathological examination found that vertebral and skull bone marrow were replaced by leukemic cells. Leukemic cells penetrated to the surface of vertebrae, forming neoplasm, and entering to the subdural space, but seldom involving in the spinal parenchyma. In the brain, leukemic cells filled in the subdural space and pia-arachnoid, covered the surface of cerebrum, cerebellum and along the virchow-robin space on the surface of pia mater, eventually invading into the brain parenchyma.SHI-1 cells could engraft in the SCI-nu/nu mice, creating an efficient and reproducible experimental model of central nervous system leukemia (CNSL) and multiorgan infiltration. This experimental model may be useful for studies on the pathogenesis of CNSL.