Abstract Background/Aims Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses. Methods 30 patients were treated with low-dose peginterferon alfa-2a (90 mug/week) and 27 patients with standard doses (180 mug/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum IP-10 levels were measured and early viral kinetic parameters were calculated. Results Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per-protocol, p=0.79 for non-inferiority). Retreatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first phase declines of viral levels and faster time to negativity. The second phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, hematologic toxicity and depression did not differ between groups. Conclusions A lower dose of peginterferon is associated with some symptomatic benefit but the response is not equivalent to standard dosing.