To analyze the profile of HBV-DNA forms in the liver in relation to different levels of virus replication, liver biopsies from 52 chronic HBsAg carriers were studied by Southern blot analysis. Quantitative evaluation of the major HBV-DNA molecules was carried out by densitometry in 27 patients with ongoing hepatitis B virus (HBV) replication in the liver. Significant variations in the intensity of the different bands were noted in individual cases, but statistical correlation between the amount of single stranded forms and levels of serum HBV-DNA was not observed. In contrast, the amount of linear 3.2 kb HBV-DNA appeared to have an inverse correlation with levels of circulating virions. Only the 3.2 kb form was detected in three patients negative for serum HBV-DNA. In these cases with 'inactive' state of episomic HBV genome seroconversion to anti-HBe occurred from 12 months before to 4 months after the time of liver biopsy testing. This 3.2 kb form can therefore be interpreted as a pattern of transition from the replicative to the non-replicative state of the virus.