Inflammation may play a central role in the pathogenesis of pulmonary arterial hypertension (PAH). Levels of interleukin (IL)-6, IL-1, C-reactive protein, regulated on activation normal T cells expressed and secreted (RANTES), and fractalkine are increased in the serum and lungs of PAH patients. Scleroderma, lupus, mixed connective tissue disease, Castleman disease, HIV, and polyneuropathy/organomegaly/endocrinopathy/M protein/skin changes (POEMS syndrome) are associated with increased IL-6 and PAH. IL-6 may play a pathogenic role through inflammation, cellular proliferation, interaction with bone morphogenetic protein pathways, decreasing prostacyclin levels, and induction of the production of other mediators such as serotonin, endothelin (ET)-1 and vascular endothelial growth factor. Experimental models of pulmonary hypertension (PH), including hypoxia and monocrotaline, are associated with increased IL-6 levels. Previous studies have found right ventricular hypertrophy (RVH) in rats treated with recombinant human IL-6. This was associated with evidence of vascular thrombosis and may be a model of chronic thromboembolic PAH. We hypothesized that IL-6 would cause PH in mice and that IL-6 may potentiate the development of PH following chronic hypoxia in mice.