C-reactive protein (CRP) is a liver-specific acute-phase protein, and its expression in hepatocyte is regulated by cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha. Although several alterations in cytokines have been found in patients with chronic viral hepatitis, it remains obscure how CRP expression is associated with progression of the disease in chronic viral infection. In the present study, CRP expression was evaluated in 45 patients with chronic hepatitis B and in 38 patients with chronic hepatitis C. By the immunohistochemical analysis, the intensity of CRP expression in hepatocyte was closely associated with the histology activity index (HAI) score in chronic hepatitis B. In contrast, the association was not found in chronic hepatitis C. When serial changes in serum levels of CRP were compared in long-term follow-up patients including 5 patients with chronic hepatitis B and 4 patients with chronic hepatitis C, serum levels of CRP fluctuated simultaneously with serum levels of alanine aminotransferase in chronic hepatitis B, whereas the correlation was not recognized in chronic hepatitis C. These results suggest that CRP expression correlates with progression of the disease in chronic hepatitis B, but not in chronic hepatitis C. It is also possible that cytokine-mediated response is more pronounced in chronic hepatitis B than in chronic hepatitis C.