BACKGROUND: The effect and applicability of interferon-based antiviral therapies in the general population of persons with hepatitis C virus (HCV) infection are unknown. OBJECTIVE: To determine the applicability and usefulness of anti-viral therapy in a metropolitan clinic population. DESIGN: Retrospective case series of consecutively referred patients. SETTING: A teaching county hospital in Cleveland, Ohio. PATIENTS: 327 patients referred to a liver clinic after a positive result for antibody against HCV on enzyme-linked immunosorbent assay (ELISA). MEASUREMENTS: Treatment rates; reasons for nontreatment. RESULTS: 34 patients had no detectable HCV RNA. Of the remaining 293 patients, 72% were not treated for the following reasons: 37% did not adhere to evaluation procedures, 34% had medical or psychiatric contraindications, 13% had ongoing substance or alcohol abuse, 11% preferred no treatment, and 5% had normal liver enzyme levels. Only 83 patients (28%) were treated; 13% had a sustained viral response. CONCLUSION: Most patients with HCV infection are not candidates for interferon-based therapies; alternative interventions should be sought for these patients.