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Interferon alpha (IFN) is the only Food and Drug Administration (FDA)-approved therapy available for the treatment of chronic hepatitis C. The ideal dose and frequency of IFN administration that produces the greatest number of patient responders with the least number of relapses following drug withdrawal remains unclear. METHODS. One hundred seventeen patients recruited over a five-year period with chronic hepatitis C were divided into four groups and treated with progressively larger doses. The rate of clinical responses defined as a loss of detectable hepatitis C virus-ribonucleic acid (HCV-RNA) in serum by polymerase chain reaction (PCR) and normalization of the serum ALT (abnormal alanine aminotransferase) for each group was calculated. RESULTS. As the dose of IFN administration increased, the response rate defined by the absence of HCV-RNA in the patient's serum after six months of follow-up increased from 7.7% to 26.6%. If the end point utilized was HCV-RNA negativity after six months of treatment, the response rate varied from 19.2% to 30%. Using the less difficult end point of a normal ALT level, the response rates varied from 32.1% to 63.3% after six months of therapy and from 10.7% to 26.7% after six months of follow-up. CONCLUSIONS. This experience demonstrates that both the response rate at the end of therapy and after six months of follow-up improves with an increase in dose of IFN administered over a six-month period.