We treated nine patients with chronic hepatitis B with recombinant interferon alpha who showed severe exacerbation of hepatitis activity. All had HBsAg for at least 5 years, and had multiple episodes of elevated serum transaminase levels. They were all men, ages 26~55 (mean 41) years. The range of serum AST was 131~885 (mean 326) U/L, the ALT 62~610 (mean 303) U/L, the bilirubin 1.3~37.3 (mean 12.0) mg/dl, total protein 4.4~8.7 (mean 6.6) g/dl, and the albumin 2.4~4.4 (mean 3, 1) g/dl. Seven patients had ascites by ultrasonogram and three showed clinical evidence of grade I hepatic encephalopathy. The needle biopsy of the liver was avalilable in 6 patients, and showed severe chronic active hepatitis with established macronodular cirrhosis. Interferon was administered in a dose of three million units subcutaneously every other day for 6 months and followed up for 12 to 24 months. The results were as follows: 1) Serum transaminases: The serum transaminases became normal in 8 patients during therapy but incresed again during the follow-up in two. One patient, whose transaminses decreased temporalily with therapy, died at the 45th days of therapy due to hepatic failure. 2) Serum bilirubin: In 7 patients with hyperbilirubinemia (2.4~37.3mg/dl), the bilirubin became normal in 5 during therapy, but incresed again in 2 during the follow up-period. In one dead case, the elevated bilirubin decreased transiently but increased again during treatment. 3) Serum albumin: In 4 patients with hypoalbuminemia, the serum albumin became normal in two, and in one became transiently elevated but decreased again during treatment. 4) Prothrombin time: In 6 patients whose prothrornbin time was prolonged, it became normal in 5 except in one patient who died. 5) Ascites: In 7 patients with ascites, the ascites disappeared in 3 during the treatment and in 3 during the follow-up period. But the ascites developed again in 2 of 6 patients. There was no change of ascites in an expired case. 6) Serum HBeAg and HBV-DNA: In 7 patients with serum HBeAg and HBV-DNA, these markers became negative in 5 during treatment, but positive again in one patient during the follow-up period. 7) Symptoms of hepatic encephalopathy: Among 3 patients who developed hepatic encephalopathy (Grade 1) before therapy, 2 patients were improved during therapy. In conclusion, this study, although not adequately controlled, suggested that alpha intreferon therapy may be effective and safe in patients with chronic hepatitis B who showed severe exacerbation of disease activity. A prospective controlled study is needed to assess the role of interferon in these patients.