Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease attempting to prevent chronicity. Almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow-up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy: none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta-analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30% to 40%) evolution to chronic hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover. (HEPATOLOGY 2002;36:S195-S200).