Acute hepatitis C often progresses to chronic infection (70%). In this clinical study, we evaluated if early treatment with peginterferon alfa-2b can prevent acute hepatitis C from developing into a chronic disease. Six patients with acute hepatitis C, based on a well-documented hepatitis C virus (HCV) seroconversion with high alanine aminotransferase (ALT) levels (> 10 x ULN) and persistent HCV RNA titers after 3 months from disease onset, were consecutively treated with peginterferon alfa-2b at 1.5 microg/kg/weekly/sc for 24 weeks. The viral load was quantified by PCR assay. Response was defined as undetectable HCV RNA and normal ALT levels at the end of therapy and after a 6-month follow-up. All patients completed therapy; at the end of therapy, 5/6 patients (83%) responded and no relapses were observed during follow-up. No correlation was found between treatment response and pretreatment viral load, viral genotype, and interval between acute infection diagnosis and start of therapy.