We prospectively followed up 821 adults with acute viral hepatitis hospitalized at the Athens Hospital for Infectious Diseases between May 1981 and May 1983. Radioimmunoassays for the detection of serologic markers of hepatitis A virus, hepatitis B virus, and hepatitis δ virus, and molecular hybridization techniques for the detection of serum hepatitis B virus deoxyribonucleic acid and hepatitis δ virus ribonucleic acid were used. Based on the results of an enzyme immunoassay for the detection of immunoglobulin M antibody to hepatitis B core antigen (Corzyme-M), 563 cases were diagnosed as acute hepatitis B and 45 as acute hepatitis superimposed on hepatitis B surface antigen carriage. Development of the hepatitis B surface antigen carrier state was observed in only 1 (0.2%) of the 507 cases with acute hepatitis B that were followed. In contrast, hepatitis B surface antigen persisted in all the latter cases. Acute hepatitis superimposed on hepatitis B surface antigen carriage was attributed to (a) hepatitis A virus superinfection in 2 (4.4%), (b) hepatitis δ virus superinfection in 22 (48.9%), (c) reactivation of chronic type B hepatitis in 12 (26.7%), (d) seroconversion from hepatitis B e antigen-positive to anti-hepatitis B e antibody-positive in 2 (4.4%), (e) presumed superinfection by non-A, non-B agent(s) in 6 (13.4%), and (f) the first clinical manifestation of chronic active hepatitis in 1 (2.2%) case. These data show that (a) acute clinical hepatitis B in adults seems to be a self-limited disease and rarely leads to the development of the carrier state in this epidemiologic setting and (b) hepatitis δ virus superinfection and spontaneous reactivation of chronic hepatitis B are the principal causes of acute hepatitis superimposed in hepatitis B surface antigen carriers in an area with a moderately high prevalence of hepatitis B virus infections.