The perception that chronic hepatitis C is an asymptomatic disease contrasts with many studies that show a strong association between chronic hepatitis C, hepatocellular cancer, and fatal liver disease. In order to resolve these issues, it is logical to directly evaluate the quality of life in patients with chronic hepatitis C and to compare this to the normal population as well as cohorts of patients with other chronic diseases. The Sickness Impact Profile was used to evaluate the impact of disease and interferon therapy on health-related quality of life in patients with chronic hepatitis C. Using this tool, patients with chronic hepatitis C had a total Sickness Impact Profile score of 9.0, compared with a score of 3.6 among the general population (P < 0.05). Patients with chronic hepatitis C also had significantly worse scores in almost every category of the Sickness Impact Profile that could be compared. However, statistically significant differences were observed only at the 24-week evaluation for work and at the end-point evaluation for the sleep and rest and recreation and pastimes categories. A more sophisticated instrument, based on the Medical Outcomes Study 36-item short-form health survey, found that patients with chronic hepatitis C scored significantly lower (P < 0.01) than the general population on each of the subscales in this survey. In addition, they scored significantly lower than patients with hypertension in seven of the subscales and two additional generic scales. Patients with chronic hepatitis C were most comparable to those with type II diabetes. A larger, more comprehensive study is underway to further evaluate these relationships.