Interferon (IFN) alpha-2a has been attached to a branched 40-kD PEG molecule and IFN alpha-2b to a linear 12-kD PEG molecule leading to elimination half-lives of approximately 75 and approximately 30 hours, respectively. In one pivotal trial, 531 patients with chronic hepatitis C were assigned to receive either 180 microg of pegylated IFN alpha-2a once weekly for 48 weeks or 3 x 6 mIU standard IFN for 12 weeks, followed by 3 x 3 mIU for 36 weeks. Sustained virological response rates were 39 and 19% for pegylated and standard IFN alpha-2a, respectively. In a second trial in patients with hepatitis C virus (HCV)-associated cirrhosis and bridging fibrosis, sustained virological response rates were 8% (3 x 3 mIU IFN three times a week), 15% (90 microg PEG-IFN alpha-2a four times a week), and 30% (180 microg PEG-IFNalpha-2a four times a week). In a third trial, 1219 patients with chronic hepatitis C were randomly assigned to receive either standard IFN alpha-2b (3 x 3 mIU) or once weekly pegylated IFN alpha-2b (0.5, 1.0, or 1.5 microg/kg). Sustained virological response rates were highest in the 1.0 microg/kg dose and achieved 25% compared with 12% in the standard IFN group. In conclusion, each regimen of pegylated IFN given once weekly is more effective than a regimen of standard IFN given three times weekly.