A prospective, non randomized trial was conducted in 22 patients with chronic hepatitis C treated for 6 months with interferon-alfa at the dose of 3 million units three times a week followed by decreasing doses for the following 6 months. Transaminase activity measurements were taken at 2, 6, 12, 18, and 24 months and a liver biopsy was performed at zero and 6 months to assess efficacy. Immunohistochemical study of HLA class I and lymphocyte subsets was performed on the biopsy specimen before and after 6 months of treatment. A complete biological response was observed in 82, 82, 60, 64 and 70 percent of patients at 2, 6, 12, 24 and 36 months, respectively. Four patients relapsed including 2 patients who suddenly stopped taking interferon-alfa. An improvement of histological features was observed in 90 percent of patients for necrosis and in 80 percent of patients for inflammation, with an overall improvement in Knodell's score reaching 85 percent. Immunohistochemical studies showed CD8+ cell infiltration already present in the area of necrosis before treatment. These tests also showed that HLA class I expression by the hepatocyte membranes was increased at 6 months and was identical in patients with or without histological improvement.