Mutant hepatitis B virus (HBV), responsible for the lack of hepatitis B virus "e" antigen (HBeAg) secretion because of a translational stop codon at nucleotide 1896 of the HBV-DNA precore region (HBeAg minus HBV), has been detected worldwide in acute and chronic HBV infections and diseases. HBeAg minus HBV appears to condition the outcome of infection and to be involved in the pathogenesis of hepatitis B. We investigated the mutant prevalence and its clinical implications in 30 hepatitis B surface antigen/HBeAg-positive children (17 treated with interferon) with chronic hepatitis B. Wild-type and HBeAg minus HBV were characterized by quantitative oligohybridization assays in sera from 29 children followed up for a mean of 33 mo (12 mo to 9 y). At admission, 18 children (62%) circulated wild-type HBV alone; mutant HBV became detectable in two of them during the follow-up before HBeAg/anti-HBe seroconversion. Wild-type and HBeAg minus HBV were detected in 10 children (34.5%); mutant HBV levels were lower than 20% of total viremia in four of them and higher in six. Serum HBV-DNA from one child did not hybridize with our probes. HBeAg minus HBV was associated with older age (p < 0.009) and higher histologic activity (p < 0.069). HBeAg/anti-HBe seroconversion occurred independently from HBeAg minus HBV detection; it was observed in six (37.5%) of 16 children with wild-type HBV alone and in four (33.3%) of 12 children with mixed viremia.(ABSTRACT TRUNCATED AT 250 WORDS)