SUMMARY: Treatment of hepatitis C virus (HCV) infection with interferon (IFN)-alpha, as monotherapy or in combination with ribavirin, is associated with significant side-effects including weight loss. The aim of our study was to describe the evolution of body weight during combination antiviral treatment and to examine the possible determinants of weight loss. This was a retrospective analysis of 126 patients who received combination therapy of pegylated IFN-alpha-2b and ribavirin at our unit. Body weight was recorded at each outpatient attendance during treatment and follow-up, and was expressed as a percentage of baseline value. We observed a decline of body weight during treatment. Median (range) weight values at 4, 12, 24, and 48 weeks (expressed as percentage of baseline weight) were 97.7 (91.5-110.2), 95.4 (84.4-109.4), 93.7 (80.8-106.5), and 91.1 (80.1-103.6) respectively. There was no significant association of increased weight loss with age, gender, pretreatment weight, ethnicity, pretreatment histological stage, cumulative IFN dose (adjusted for body weight), HCV genotype or treatment outcome. Median body weight returned to baseline within 6 months of stopping treatment. Patients experience significant weight loss during combination therapy. Those experiencing greater weight losses during therapy did not benefit from improved antiviral response.