We have examined serological markers of replicative and nonreplicative infection in 124 adult, black South African carriers of hepatitis B virus (HBV), in whom this infection is predominantly acquired in early childhood. The mean age of the group was 36 years. Antibody to hepatitis Be antigen (anti-HBe) was present in the serum of 93.5% of these carriers. Only 25.8% of the carriers were positive for HBV DNA in serum, and in the majority of these only trace amounts were detectable. IgM antibody to hepatitis B core antigen (IgM anti-HBc) was negative in 54% of the carriers, and only 26% had IgM anti-HBc in high titer. A significantly greater proportion of carriers who were positive for anti-HBe were positive for IgM anti-HBc (43.1%)than were positive for HBVDNA (24.5%). Serum aminotransferases were less than twofold elevated in 90.3% of the carriers. Only one carrier has thus far developed hepatocellular carcinoma. These results suggest that there is an inexorable progression to predominantly nonreplicative infection in the majority of southern African adult, black carriers, an occurrence that may take several decades. In areas endemic for HBV infection, antiviral agents effective against replicative HBV will have to be administered in childhood.