OBJECTIVE To investigate the histological changes in liver biopsies and HBV DNA changes in sera induced by 18 weeks of interferon alpha-2b therapy in patients with chronic hepatitis B infection. METHODS Twenty-two patients were enrolled into this prospective study. All patients had a liver biopsy within 1 week before starting interferon therapy. Interferon alpha-2b was given at a dose of 3MU thrice a week for 18 weeks. A second liver biopsy was taken for comparison at the end of week 18. Blinded biopsies were scored according to Knodell's histology activity index (HAI), and examined for HBsAg, HBeAg, HBcAg and alpha - SMA by immunohistochemistry. The serum samples corresponding with liver biopsies were collected and HBV DNA, e-antigen were measured. RESULTS Histological assessment revealed a significant improvement in intralobular inflammation and periportal necrosis after treatment(P<0.01). Fifty-five percent (12/22) patients had a reduction of hepatic necroinflammatory HAI score at the end of 18 weeks of interferon alpha-2b therapy compared to pretreatment values, but periportal inflammation and fibrosis failed to show improvement. HBeAg disappeared from liver tissues in 7 from 13 cases(53.8%)and a significant reduction of activated liver stellate cells was demonstrated in biopsies performed after suspending the interferon treatment(P=0.0004). Serum HBV DNA levels decreased significantly after treatment (P<0.01). The clearance rate of HBeAg was 42.9% after treatment. There was no significant difference between HBeAg positive and negative patients either in liver histological improvements or declining level of serum HBV DNA. CONCLUSIONS Interferon alpha-2b may decrease the level of serum HBV DNA in the patients with chronic hepatitis B infection, and improve their necroinflammation in liver tissues.