A case-control study was carried out comparing 333 case subjects with non-A, non-B hepatitis and 1095 hospital control subjects. Of 333 case subjects, 197 (59%) were positive for hepatitis C antibody (anti-HCV). Excluding blood transfusion and intravenous drug use, surgical intervention and dental therapy were strongly associated with anti-HCV-positive cases: in particular, obstetric and gynecology surgical intervention was found to be strongly associated with HCV positivity (odds ratio [OR] = 32; 95% confidence interval [CI] = 7, 147). Raw shellfish consumption was a risk factor for anti-HCV-negative cases (OR = 2.2; 95% CI = 1.0, 5.1), thus suggesting an enterically transmitted virus in sporadic non-A, non-B hepatitis in Italy.