Objective: To evaluate the serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, tumor growth factor (TGF)-β, endothelin, and immunoglobulin (Ig)E in patients with idiopathic epistaxis, compared with healthy control individuals. Methods: Serum levels of IL-6, IL-8, TNF-α, TGF-β, endothelin, and IgE were evaluated in 110 patients with idiopathic epistaxis and 100 healthy controls using the enzyme-linked immunosorbent assay (ELISA) technique. Results: Serum levels of IL-6 (P <.001) and TGF-β (P = .001) were significantly increased in patients with idiopathic epistaxis, compared with controls. TNF-α serum levels were significantly increased in male patients, compared with female patients (P = .053). We observed decreased antihistamine levels and increased expression of TGF-β (P = .02) and TNF-α (P = .02), respectively. Conclusions: IL-6 and TGF-β appear to participate in the pathogenesis of idiopathic epistaxis. TNF-α may be considered a risk factor for male patients in developing epistaxis. Antihistamines may inhibit angiogenesis by decreasing expression of TGF-β and increasing expression of TNF-α.