Pegylated IFN-alpha(2a) (PEG-IFN-alpha(2a) [40 kDa]; Pegasys, Hoffmann-La Roche) is a new subcutaneous formulation of IFN-alpha(2a), produced by its attachment to a 40 kDa branched polyethylene glycol moiety by a stable amide bond. PEG-IFN-alpha(2a) 180 micro g once-weekly has enhanced pharmacokinetic and pharmacodynamic properties which translate into significantly improved efficacy and similar safety and tolerability compared with IFN-alpha in patients with chronic hepatitis C even with underlying cirrhosis. The combination of PEG-IFN-alpha(2a) (40 kDa) plus ribavirin produces significantly better sustained virological responses than the combination of IFN-alpha(2b) and ribavirin, while it is accompanied by a similar or even lower incidence of adverse events and better quality of life. PEG-IFN-alpha(2a) (40 kDa) is the first pegylated IFN-alpha for which evidence-based recommendations can be made on optimum therapy duration and ribavirin dose according to HCV genotype. PEG-IFN-alpha(2a) (40 kDa) is expected to improve the efficacy and tolerability of treatment for chronic hepatitis C.