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 interferon/ribavirin 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.