Approximately 30% of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels and another 40% have ALT levels that are less than twice the upper limit of the normal range. Most patients with normal ALT levels have mild degrees of inflammation with mild or no fibrosis, and the rate of disease progression is reduced compared with that in patients with elevated ALT levels. Some patients with normal ALT levels have advanced fibrosis and cirrhosis on liver biopsy. Treatment of patients with normal ALT levels with either interferon monotherapy or interferodribavirin combination therapy has shown sustained virological response (SVR) rates that are equivalent to those achieved for patients with elevated ALT levels. Thus, patients with chronic hepatitis C should not be excluded from therapy based on ALT levels alone. The decision to initiate therapy with interferon and ribavirin should be based on a combination of factors independent of ALT levels including amount of fibrosis on liver biopsy, hepatitis C virus (HCV) genotype and viral level, patient age and motivation, and co-morbid illness, and the presence of other complicating conditions. (HEPATOLOGY 2002;36:S179-S184.) t the 1997 National Institutes of Health Consensus Development Conference on "Management A of Hepatitis C," the Consensus Panel concluded that alpha interferon treatment could not be recommended for patients with persistently normal alanine aminotransferase (ALT) levels and that therapy might actually worsen the course of disease.' This recommendation led to exclusion of patients with normal ALT levels from routine therapy, and helped support the continued exclusion of these patients from the pivotal trials of evolving therapy for this disease. Since that time there has been progress in the understanding of the clinical significance of normal ALT levels in chronic hepatitis C,2-6 and the completion of several small clinical trials of newer ap-Abbreviations: A L E ahnine aminotransferase; SVR, sustained virological response; HCK hepatitis C virus; ASZaspartate aminotransferase.