Antibody responses to the GOR epitope and hepatitis C virus (HCV) core were investigated in 136 patients with chronic HCV infection. Patient age (P = .011) and necroinflammatory activity (P < .001) were significantly greater in 92 (67.6%) patients with anti-GOR than in 44 (32.4%) patients without anti-GOR. HCV RNA concentration was significantly higher in patients with anti-GOR (P = .031). HCV 1a or 1b genotypes were also found according to anti-GOR status. GOR and HCV core (amino acids 5-19) antibody responses correlated significantly (rs = .615, P < .001). Anti-HCV core(5-19) was detected in 67 (73%) of 92 patients with and in 14 (32%) of 44 without anti-GOR (P < .001). Patients with concurrent anti-GOR and anti-HCV core(5-19) had significantly greater necroinflammatory activity (P = .003). By multivariate analysis, anti-HCV core(5-19), patient age, and necroinflammatory activity were correlated with anti-GOR response (P < .001). Reactivity to the GOR autoepitope correlates with HCV core response and liver necroinflammatory activity, thus suggesting an immunopathogenic role in chronic hepatitis C.