['Chronic hepatitis C (CHC) patients selected for entry into treatment trials have been reported to have impaired health-related quality of life (HRQOL). However, these trials have an inherent selection bias, and HRQOL in CHC patients may have been underestimated because of the exclusion of patients with comorbid illness. The aim of this study was to assess HRQOL in an unselected group of CHC patients and to identify factors associated with impairment in HRQOL.', 'A total of 220 consecutive eligible CHC patients were enrolled from a hepatology clinic. HRQOL was assessed by the short form 36 (SF-36) and comorbid illnesses were assessed by an interview.', 'CHC patients had significantly lower SF-36 scores in all subscales and in the summary scales when compared to those of the healthy general population in the United States (p < 0.001). Compared to CHC patients entering treatment trials, our patients had lower SF-36 scores on five subscales (p < 0.001). The presence of comorbid illness was the most important predictor of HRQOL in CHC patients. However, CHC alone resulted in significantly lower SF-36 scores in all subscales and summary scales (p < or = 0.003) compared to those of the healthy U.S. population. There was no correlation between SF-36 scores and history of i.v. drug use or dependence. alcohol dependence. and serum aminotransferase levels.'] Is comorbid illness an important determinant of health-related quality of life in patients with chronic hepatitis C?