The efficacy of interferon (IFN) therapy for chronic hepatitis C is dependent on compliance. Anorexia is an important adverse effect in determining compliance. To clarify the mechanisms underlying anorexia, the level of ghrelin was determined during therapy. Fourteen patients with chronic hepatitis C received IFN-alpha2b with or without ribavirin (Rib+ or Rib- group; n=7 in each group) for 24 weeks. Serum ghrelin concentrations and body weight were determined before, 2 and 24 weeks after initiation of therapy. Serum ghrelin concentrations and body weight significantly decreased 2 weeks after initiation of therapy (P=0.0008 and 0.0062, respectively), and then returned to the level before therapy. The Deltaghrelin concentration correlated with Deltabody weight after 2 weeks (r=0.726, P=0.023). Percentage reduction of serum ghrelin was significantly higher in the Rib+ group than in the Rib- group (P=0.046). Percentage reduction in body weight tended to be higher in the Rib+ group (P=0.057). IFN-alpha2b therapy causes short-term reduction of serum ghrelin and body weight, and this may occur to a greater extent with combination therapy. Reduction of serum ghrelin might contribute partly to anorexia, leading to weight loss.