Determination of hepatitis B virus DNA in serum using the polymerase chain reaction: clinical significance and correlation with serological and biochemical markers. Sera from 98 patients with various stages of chronic hepatitis B virus infection were studied to determine the clinical significance of hepatitis B virus DNA in serum detected by the polymerase chain reaction. Patients were divided into three groups according to their HBsAg and HBeAg status. Group I (n = 31) had detectable HBsAg and HBeAg, group II (n = 46) had HBsAg but not HBeAg and group III (n = 21) consisted of patients who were once chronic hepatitis B virus carriers but had lost HBsAg during follow-up. Group I patients usually had significant liver disease (raised serum aminotransferases), had higher titers of HBsAg and had been infected with hepatitis B virus for a shorter period than patients in the other two groups. All patients in group I had hepatitis B virus DNA detectable by polymerase chain reaction and 94% had sufficient hepatitis B virus DNA present for detection by dot-blot hybridization. Group II patients had lower mean serum aminotransferase activities and titers of HBsAg than those in group I. Serum hepatitis B virus DNA was detectable by polymerase chain reaction in 78% but in only 30% of group II patients by dot-blot hybridization. Group II patients who did not have hepatitis B virus DNA detectable by polymerase chain reaction had mean serum aminotransferase levels within the normal range and had a younger mean age than those with hepatitis B virus DNA. Group III patients generally had no evidence of active liver disease. 