Atherosclerosis and post-transplant graft arteriosclerosis are both characterized by expansion of the arterial intima as a result of the infiltration of mononuclear leukocytes, the proliferation of vascular smooth muscle cells (VSMCs) and the accumulation of extracellular matrix^,,. They are also associated with the presence of the immunomodulatory cytokine interferon-γ (IFN-γ)^,. Moreover, in mouse models of atheroma formation or allogeneic transplantation, the serological neutralization or genetic absence^,,, of IFN-γ markedly reduces the extent of intimal expansion. However, other studies have found that exogenous IFN-γ inhibits cultured VSMC proliferation^,,,,, and matrix synthesis, and reduces intimal expansion in response to mechanical injury^,,. This discrepancy is generally explained by the idea that IFN-γ either directly activates macrophages, or, by increasing antigen presentation, indirectly activates T cells within the lesions of atherosclerosis and graft arteriosclerosis. These activated leukocytes are thought to express the VSMC-activating cytokines^,, and cell-surface molecules that cause the observed arteriosclerotic responses. Here we have inserted pig and human arteries into the aorta of immunodeficient mice, and we show that IFN-γ can induce arteriosclerotic changes in the absence of detectable immunocytes by acting on VSMCs to potentiate growth-factor-induced mitogenesis.