Sera from 31 HBsAg-positive Chinese patients with inoperable hepatocellular carcinoma (HCC) were tested for hepatitis B virus DNA (HBV DNA) by means of dot hybridisation and Southern blot technique. HBV DNA probes were prepared from human plasma. Eighteen of the patients were HBeAb-positive, 12 were HBeAg-positive and one case had neither marker. Serial specimens were obtained from 16 cases over 5-42 weeks, while the patients were treated with recombinant leukocyte A interferon (rIFN-A) or adriamycin. Seven patients (2 HBeAg-positive, 5 HBeAb-positive) were positive for HBV DNA. In two patients HBV DNA and HBV DNA polymerase (DNAp) appeared in serum weeks after rIFN-A or adriamycin treatment was started. In two other cases, HBV DNA that was initially present disappeared during rIFN-A treatment. In a fifth patient HBV DNA persisting after adriamycin treatment diminished after change of treatment to rIFN-A. With one possible exception the HBV DNA detectable by Southern blot technique was composed chiefly of sequences 2.2-3.2 kb size indicating the presence of unintegrated DNA forms. DNAp activities were raised in the presence of HBV DNA in 4 patients. These findings show that HBV replication can be activated or suppressed in advanced HCC. Treatment with rIFN-A may have been effective in suppressing HBV DNA synthesis, but the number of cases studied was too small to arrive at a definite conclusion on this point.