The relationship of the presence of hepatitis B virus (HBV) DNA in serum, a measure of HBV-replication, to HBeAg/anti-HBe status has been examined. In Northern Europe, there is a strong positive correlation between the presence of HBV-DNA and HBe antigenaemia and a negative correlation with the presence of anti-HBe. These associations are less marked in patients from Southern Europe, Africa, the Middle and Far East. When HBV-DNA is present in the serum of anti-HBe carriers, it is usually associated with the presence of severe liver disease or carcinoma. Forty percent of patients with hepatocellular carcinoma had evidence of continuing HBV replication.