The aim of this study was to examine the effects of diagnosis of hepatitis C virus (HCV) infection on quality of life in a cohort admitted to Fairfield Infectious Diseases Hospital with acute hepatitis from 1971 to 1975. Sera stored from the original admission were tested for antibody to HCV. Systematic approaches were used to locate anti-HCV–positive individuals and outcomes assessed by the Short Form 36 (SF-36) scale and a study-specific questionnaire as well as clinical review. Study subjects' SF-36 scores were compared with Australian population norms. Anti-HCV and HCV-RNA positive individuals (n = 15) aware of their serostatus rated significantly worse on 7 of 8 SF-36 scales compared with population norms. However, HCV-seropositive and RNA-positive individuals unaware of their HCV serostatus (n = 19) scored significantly worse in only 3 scales. Those aware of their serostatus did not differ sociodemographically, clinically, virologically, or serologically from those who were unaware, nor was there a link between quality of life (QOL) scores and objective measures of ill health. All subjects had injected drugs in the past. In conclusion, HCV-RNA and anti-HCV–positive individuals in our study have significantly poorer subjective health status 26 years after original infection compared with population norms. QOL measures were significantly worse for HCV-seropositive individuals aware of their serostatus compared with those unaware. We feel that the reduced QOL in the diagnosed group may be partially an effect of labeling and that the impact of the diagnostic processper seon QOL in individuals with HCV requires further evaluation.