ABSTRACT— To examine the relationship between changes of serum hepatitis B virus-dexoyribonucleic acid (HBV-DNA) and transaminase levels during acute exacerbation of chronic type B hepatitis, serial serum specimens from 74 patients were assayed for HBV-DNA by slot blot hybridization with 32P-labeled cloned HBV-DNA as probe. Of these patients, serial serum specimens were obtained with an interval of 2–7 days in 22 patients (Group I), 8–14 days in 30 patients (Group II) and 15–30 days in 22 patients (Group III). The peak of serum HBV-DNA was reached shortly before or simultaneously with the maximum elevation of serum alanine transaminase (ALT) in most (>90%) of the acute exacerbations. In contrast, the peak of serum ALT was reached before maximum elevation of serum HBV-DNA in only 13.6% of Group I, 3.3% of Group II and 13.6% of Group III (9.5% of whole series). The results suggest that the increase of serum HBV-DNA is an event preceding, rather than the result of, hepatocytolysis in most of the acute exacerbations occurring in patients with chronic type B hepatitis.