We enrolled 44 patients with hepatitis B virus (HBV) acute infection, 21 anti-hepatitis C virus (HCV)–positive for at least 1 year (case BC group), 20 anti-HCV–negative (control B group), and 3 with HBV/HCV acute concurrent infection. For each case BC, a subject with chronic HCV infection alone was selected (control C group). At the first observation, 85.7% of patients in case BC group and 85% of those in control B group were HBV-DNA–positive (polymerase chain reaction [PCR]), with a similar trend towards a decrease and negativization in about 20 days; in the case BC group, seroconversion to antibody to hepatitis B e antigen (anti-HBe) was more rapid. HCV-RNA (PCR) was undetectable in all case BC patients but 1, who shortly became negative, whereas 85.7% of subjects in control C group were positive (P < .001). Severe acute hepatitis was more frequent in the case BC group than in the control B group (28.6% vs. 0%, P < .05). Of the 14 patients in the case BC group and of the 16 in the control B group followed up for more than 6 months, 1 in the first and 1 in the second group became hepatitis B surface angiten (HBsAg) chronic carriers. Of the 13 patients in case BC group who recovered, 1 cleared both anti-HCV and HCV-RNA, 6 became HCV-RNA–positive, and 6 remained HCV-RNA–negative. In patients with HBV/HCV acute concurrent infection, HBV-DNA became undetectable in 15 days, and HCV-RNA and anti-HCV became positive at days 30 and 45, respectively; these patients developed HCV-RNA–positive chronic hepatitis. In conclusion, HBV superinfection in chronic HCV carriers has a severe clinical course and strongly and persistently depresses HCV.