Increasing interest continues to focus on the possibility that viral infection of the vessel wall can initiate and maintain human vascular disease. While virus is usually cleared from most affected sites, Del Canto and colleagues now report that viruses may evade the immune system by establishing themselves in a protected niche provided by the elastic media of large arteries. Chronic infection then leads to a destructive arteritis associated with a neutrophilic infiltrate. Of note, immunoprivilege arises as a counterproductive consequence of the ability of the elastic media to specifically exclude infiltrating T cells and macrophages. The means by which mononuclear cells, but not neutrophils, are prevented from invading the media remains to be determined, but experiments performed in either interferon-g (IFNg)-depleted or IFNg-receptor-deleted mice clearly establish a role for the cytokine in disease progression. Bone marrow transplants into wild-type or IFNg-receptor knockout mice further demonstrate that IFNg limits medial infection as well as disease severity by affecting somatic as well as hematopoietic cell function. Given reports emphasizing the ability of IFNg to promote vascular pathology in other settings such as arteriosclerosis, this cytokine has recently been considered as a new target for therapeutic intervention. However, as demonstrated in the current study, attempts to intercept IFNg must be considered carefully as vessel wall disease could be exacerbated depending on the underlying initiating event.