To compare the epidemiology of hepatitis B virus (HBV) with hepatitis C virus (HCV) in a southern Sudanese population, 666 out-patients attending 6 public clinics in the city of Juba were enrolled in a serosurvey. The average age of subjects was 16 years; 54% were female. Of the 651 samples tested for hepatitis B markers, HBsAg was found in 26% and anti-HBc in 67%. In contrast, only 21 (3%) of the 666 samples were positive for anti-HCV using a second generation immunoblot assay (RIBA-2). Seventeen (81%) of the 21 anti-HCV-positive subjects were positive for anti-HBc, compared to 66% (418/630) of subjects negative for anti-HCV (P = 0.07). None of the anti-HCV-positive subjects reported receiving a prior blood transfusion and only 5 subjects reported a history of jaundice. Nine of the 21 (43%) anti-HCV-positive subjects reported a history of scarification, compared to 23% (148/645) of anti-HCV-negative subjects (P = 0.01). Hepatitis B infection was also associated with scarification by univariate analysis. However, after adjustment for age a history of scarification was not significantly associated with hepatitis C infection, but it was with HBV infection (odds ratio = 1.5, 95% CI 1.0-2.5; P = 0.05). The findings of this study indicate that HCV infection is not highly endemic in this population and that the epidemiology of HCV differs from that of HBV.