Summary. Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing α-interferon (3 MU thrice weekly) + ribavirin (1000–1200 mg/day) for 48 weeks with no treatment in treatment naïve, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with α-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18%vs 49%P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.