Interferon and pegylated interferon (peg-IFN) are highly effective in patients with acute hepatitis caused by hepatitis C virus (acute hepatitis C, AHC), but the optimal timing of treatment is still under debate. In this open-labelled, uncontrolled trial, 19 patients with AHC, including 12 intravenous drug users (IVDUs), were treated early in the course of the infection with peg-IFN-alpha2b for 12 weeks. Diagnosis was made according to standardized criteria. The HCV RNA decay was analysed during the first 4 weeks of treatment by quantitative branched-DNA and by qualitative RT-PCR. Of the patients, 11 (58%) had genotype 1. Sustained virological response (SVR) was achieved in 14 out of 19 patients (74%) and the mean time to achieve a negative RT-PCR for HCV RNA was 2.5 weeks. The SVR was associated by univariate analysis with peg-IFN dosage < or = 1.33 microg/kg/week (P = 0.026) and HCV RNA level at onset of therapy (P = 0.017). Using a logistic regression model, only peg-IFN dosage > or = 1.33 microg/kg/weekly was significantly associated with SVR (P = 0.0379, OR: 14.7; 95% CI: 1.16-185.2). The SVR was 100% and 83.3%, respectively, in genotype 1 and non-1 infected patients treated with a dosage equal to or higher than 1.33 microg/kg, compared with 40% and 50%, respectively, in those who received a lower dosage. Efforts should be made to propose a 12-week treatment with peg-IFN-alpha2b for AHC, and to maximize peg-IFN dosage. Early treatment is associated with early disappearance of HCV RNA.