OBJECTIVE Because outcome of antiviral treatment in patients with chronic hepatitis (CH) B is difficult to predict, we compared the severity of hepatitis with serum hepatitis B virus (HBV) DNA concentration. METHODS We studied 40 HBV carriers with distinct stages of chronic infection, 32 HBe antigen (HBeAg)-negative or low-grade positive carriers whose HBV strains did not contain a point mutation at nucleotide 1896, 37 HBeAg-negative carriers with or without hepatitis, and 51 HBeAg-positive CH patients treated with interferon. Serum HBV DNA concentration was measured by the end-point dilution method using a polymerase chain reaction (PCR). The point mutation at nucleotide 1896 was detected by restriction fragment length polymorphism with PCR. RESULTS Among the stages of chronic HBV infection, the serum HBV DNA concentration was lowest (10(0.67 +/- 0.71) copies/microliter) in HBeAg-negative asymptomatic carriers. A low-level viremia (10(2.10 +/- 1.45) copies/microliter) of HBV strains without the mutation at nucleotide 1896 was associated with an HBeAg-negative state. In HBeAg-negative carriers, the serum HBV DNA concentration in those without hepatitis was significantly lower than in those with hepatitis (10(1.00 +/- 0.89) vs 10(3.31 +/- 1.25) copies/microliter, p < 0.0001); 20 of 21 asymptomatic carriers had an HBV DNA concentration below 10(2) copies/microliter. Patients with serum HBV DNA concentrations below 10(1) copies/microliter. at the end of interferon treatment maintained normal serum alanine aminotransferase concentrations. CONCLUSIONS A serum HBV DNA concentration below 10(1) copies/ microliter is an important goal for successful treatment of CH-B. PCR is necessary to assess such low-level viremias.