To clarify the status of HBV in serum of chronic hepatitis B (CHB) patients who were treated with alpha-interferon, we determined the serum HBV DNA before and after treatment in 15 CHB patients with polymerase chain reaction (PCR). Before treatment all the 15 patients were HBsAg and HBeAg positive. HBV DNA was also positive with dot-blot hybridization (DB), PCR, ethidium bromide (PCR-EB) and PCR Southern-blot hybridization (PCR-SBH). HBeAb was negative in all the 15 patients. 12 patients has the determination repeated 2 to 39 weeks after treatment, 7 out of the 12 patients became HBeAg negative and HBV DNA also negative with DB and PCR-EB. However, in 5 of the 7 patients HBV DNA was still positive with PCR-SBH. Seroconversion of HBeAb from negative to positive occurred in 4 of the 12, but HBV DNA of the 4 patients remained positive with PCR-SBH. After an interval of one and half year or more following treatment 12 patients repeated the examination, only 5 of the 12 patients became seronegative for HBeAg and HBV DNA with DB and PCR-EB, but in 4 of the 5 HBV DNA was positive with PCR-SBH. Two of the 5 were seropositive for HBeAb and HBV DNA with PCR-SBH. The mechanism of residual viraemia after alpha-interferon treatment in CHB patients is uncertain.