Sixty percent of patients fail to respond to interferon monotherapy. African-Americans with hepatitis C appear to respond less well to interferon monotherapy. Retreatment with a higher dose of consensus interferon for 48 weeks has led to a sustained virologic response rate of 13%. As a group, interferon nonresponders who breakthrough while on interferon monotherapy seem to have a more favorable response rate to a repeat course of treatment. Retreatment with interferon and ribavirin for 6 months in nonresponders led to a sustained virologic response rate of 21%. Preliminary results from two trials in the United States demonstrate similar treatment efficacy. There is now evidence that maintenance interferon therapy may also be beneficial in interferon monotherapy nonresponders.