Angiogenesis is an essential factor in the growth and progression of hematological malignancies including multiple myeloma (MM). Vascular endothelial growth factor and its receptors have been shown to be targets for treating tumors. This study explores the effect of adenovirus-mediated delivery of soluble vascular endothelial growth factor receptor Fms-like tyrosine kinase-1 (sFLT-1) on the growth of MM cell line KM3 in nude mice. sFLT-1 cDNA was amplified by reverse transcription-polymerase chain reaction from human umbilical vein endothelial cells and was used as a transgene to construct an adenoviral vector carrying sFLT-1 (ADV-sFLT). Cell proliferation and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays were carried out to evaluate the effect of ADV-sFLT on human umbilical vein endothelial cells and KM3 cells in vitro. Eighteen female BALB/c nude mice were inoculated subcutaneously with KM3 cells, and they were randomly divided into three groups and injected intravenously with ADV-sFLT, ADV-LacZ, or phosphate-buffered saline (PBS). The volume of KM3 xenografts was measured twice a week. Three weeks after the initial treatment, the volume of MM xenografts in the mice treated with ADV-sFLT, ADV-LacZ, or PBS was 770.32+/-28.73 mm3, 1983.36+/-43.72 mm3, and 2042.05+/-82.31 mm3, respectively (P<0.01, ADV-sFLT versus ADV-LacZ or PBS). The value of microvessel density was 29.17+/-6.85, 79.17+/-7.35, and 78.83+/-8.54 in the tumors treated with ADV-sFLT, ADV-LacZ, and PBS, respectively (P<0.01, ADV-sFLT versus ADV-LacZ or PBS). This study suggested that the adenovirus-mediated sFLT-1 gene greatly inhibits MM-derived tumor growth and angiogenesis in mouse xenograft, and might serve as a new therapy for MM.