The increased frequency of autoantibodies and B cell non-Hodgkins lymphoma (B-NHL) in hepatitis C virus (HCV) infection suggests dysregulated humoral immunity. Soluble CD23 (sCD23) is involved in B cell activation and proliferation and the serum levels are raised in autoimmune diseases and B cell lymphoproliferative disease. We compared the serum levels of sCD23 in patients with HCV infection with those in patients with alcoholic cirrhosis (AC) and in healthy controls. Serum levels of interleukin (IL) 8, IL10, granulocyte macrophage-colony stimulating factor, and interferon-gamma were assessed simultaneously to check for generalized nonspecific immune stimulation. In contrast to the essentially normal serum levels of these latter cytokines, the levels of sCD23 were raised in the patients with HCV compared to those with AC and the normal controls (medians 34.0, 10.1, and 11.1 arbitrary units, respectively; HCV vs AC P < 0.0004, HCV vs controls P < 0.0001, AC vs controls P > 0.8). These results confirm HCV-induced humoral immune dysregulation and invite comparison with primary Sjögrens syndrome and Epstein-Barr virus infection, both of which are also associated with raised levels of serum sCD23, autoantibodies, and B-NHL.