Up to 25% of patients with chronic hepatitis C have persistently normal serum alanine aminotransferase (ALT) levels. Reports from some studies indicate that patients with normal ALT levels are more likely to be female and nondrinkers. Patients with persistently normal aminotransferase levels often have mild disease on liver biopsy with little or no fibrosis, but a small number of patients may have substantial fibrosis or cirrhosis. Treatment with interferon monotherapy has been disappointing. Combination therapy with interferon and ribavirin is controversial, but early clinical results have shown good response rates. Currently, therapy for chronic HCV patients with normal ALT levels should be based upon results from liver biopsy and preferably be done in the context of a clinical trial.