Combination therapy with subcutaneous peginterferon alpha-2a (40KD) [Pegasys] plus oral ribavirin (Copegus) has been evaluated previously in patients with chronic hepatitis C and elevated ALT levels. A recent randomised, nonblind, multicentre trial examined the efficacy of this combination therapy in the treatment of patients with persistently 'normal' ALT levels. These trial results showed that combination therapy with peginterferon alpha-2a (40KD) plus ribavirin is effective in patients with chronic hepatitis C and persistently normal ALT levels. Overall, a sustained virological response occurred in over 50% of patients who received combination therapy for 48 weeks, albeit with a low daily dosage of ribavirin. The tolerability profile of combination therapy in patients with persistently normal ALT levels is similar to that seen in patients with elevated ALT levels. The decision as to whether or not treatment should be initiated in patients with chronic hepatitis C and persistently normal ALT levels should be made on an individual basis. If a decision is made to treat, combination therapy with peginterferon alpha-2a (40KD) plus ribavirin can be considered a first-line treatment option.