Interferon and ribavirin combination therapy for chronic hepatitis C produces a number of well-described side effects that are dominated by fatigue, influenza-like symptoms, hematologic abnormalities, and neuropsychiatric symptoms. Combination therapy with pegylated interferons (peginterferon alfa-2a and dfa-2b) yields an adverse event profile similar to standard interferon, although the frequency of certain adverse events may vary by preparation. Premature withdrawal from therapy due to adverse events was required in 10% to 14% of participants in registration trials of these agents. Most adverse events were safely and effectively managed by dose reduction using predetermined criteria. The most common indications for dose reduction were hematologic abnormalities, such as anemia and neutropenia, with the latter more frequent in peginterferon treatment arms. Recent data suggest that maintaining adherence to a prescribed treatment regimen can enhance antiviral response. Strategies to maximize adherence are being developed and, in the future, may include early identification of and therapy for depression and the selective use of hematopoietic growth factors to ameliorate hematologic abnormalities. (HEPATOLOGY 2002;36: S237-S244.) he side effect profile of combination therapy using standard interferon and ribavirin has been T well described. 1-4 The major types of side effects include fatigue, influenza-like symptoms, gastrointestinal disturbances, neuropsychiatric symptoms, and hematologic abnormalities.1.2 These side effects may be treatment limiting and require dose reduction or drug discontinua-ti0n.3,~ Numerous other side effects occur with lower frequencies but may still have an impact on the tolerability of antiviral therapy.2 Pegylated interferons (peginterferon alfa-2a and peginterferon alfa-2b) have significantly improved pharmacokinetics,5-8 resulting in improved antiviral efficacy, which also has the potential to alter the side effect profile. This review will focus on the frequency and management of side effects reported with the use of peginterferon and ribavirin for the treatment of chronic hepatitis C based on data from 2 large registration trials that