Angiomatous lesions are common in infants and children. Hemangioendotheliomas (HE) represent one type of these lesions. Endothelial cell proliferation and development of vascular/blood cell filled spaces are inherent in the growth of HE. Therefore, understanding mechanisms that regulate the proliferation of these lesions should provide key insight into mechanisms regulating angiogenesis. A murine model was used to test the significance of MCP-1 in HE proliferation. EOMA cells, derived from a spontaneously arising murine HE, generate these lesions with 100% efficiency when injected subcutaneously into syngeneic mice. MCP-1 produced by EOMA cells recruit macrophages, which were shown to induce angiogenic behavior in EOMA cells by stimulating trans-well migration and inducing sprout formation on type I collagen gels. When EOMA cells were injected into MCP-1^-/- mice only 50% of the mice developed tumors, presumably because the low levels of MCP-1 expressed by the injected EOMA cells were enough to overcome any host deficits of this chemokine. When EOMA cells were co-injected with a neutralizing antibody to MCP-1, tumors failed to develop in any of the treated mice including syngeneic 129 P/3, C57 BL/6 (wt) and MCP-1^-/-. These results present first evidence that MCP-1 is required for HE proliferation and may promote growth of these lesions by stimulating angiogenic behavior of endothelial cells. The current report constitutes the first in vivo evidence demonstrating a complete response for any neoplasm, and specifically a vascular proliferative lesion, to anti-MCP-1 therapy in animals with an intact immune system.