Peginterferon-α-2a (40KD) is a new ‘pegylated’ subcutaneous formulation of interferon-α-2a that has been developed to improve on the pharmacokinetic profile and therapeutic efficacy of interferon-α-2a. Peginterferon-α−2a (40KD) is produced by the covalent attachment of recombinant interferon-α-2a to a branched mobile 40KD polyethylene glycol moiety, which shields the interferon-α-2a molecule from enzymatic degradation, reduces systemic clearance and enables once-weekly administration.Peginterferon-α-2a (40KD) was significantly more effective than interferon-α-2a in interferon-α therapy-naive adults with chronic hepatitis C in three nonblind, randomised, multicentre trials. Virological responses (intention-to-treat results) were achieved in 44 to 69% of patients with or without cirrhosis after 48 weeks of treatment with peginterferon-α-2a (40KD) 180 µg/week; sustained virological responses 24 weeks after the end of treatment occurred in 30 to 39% of patients. Virological responses at the end of treatment and at long-term follow-up were significantly higher than those achieved with interferon-α-2a. Peginterferon-α-2a (40KD) was significantly more effective than interferon-α in patients with or without cirrhosis infected with HCV genotype 1.Sustained biochemical responses achieved with peginterferon-α-2a (40KD) 180 µg/week ranged from 34 to 45% and were significantly higher than with interferon-α-2a. Recipients of peginterferon-α-2a (40KD) also experienced histological improvements; 24 weeks after discontinuation of treatment with peginterferon-α-2a (40KD) 180 µg/week, 54% to 63% of patients had a ≥2-point improvement in histological activity index score. Peginterferon-α-2a (40KD) produced histological responses in patients (with or without cirrhosis) with or without a sustained virological response.Peginterferon-α-2a (40KD) produced better results than interferon-α-2a alone or interferon-α-2b plus oral ribavirin on various measures of quality of life in patients with chronic hepatitis C.The tolerability profile of peginterferon-α-2a (40KD) is broadly similar to that of interferon-α-2a in patients with chronic hepatitis C with or without cirrhosis. Headache, fatigue and myalgia are among the most common adverse events.In conclusion, peginterferon-α-2a (40KD) administered once weekly produces significantly higher sustained responses, without compromising tolerability, than interferon-α-2a administered thrice weekly in noncirrhotic or cirrhotic patients with chronic hepatitis C, including those infected with HCV genotype 1 - a group in whom interferon-α treatment has usually been unsuccessful. Peginterferon-α-2a (40KD) is a valuable new treatment option and appears poised to play an important role in the first-line treatment of patients with chronic hepatitis C, including difficult-to-treat patients such as those with compensated cirrhosis and/or those infected with HCV genotype 1.