Objective  To study the effects of mutations in the core promoter (CP) and the precore/core gene of hepatitis B virus ( HBV) on acute clinical exacerbation in chronic asymptomatic HBV carriers(AsC) and the severity of chronic hepatitis B.Methods  CP and precore/core gene were sequenced directly from sera of four AsCs,twenty  seven patients with chronic hepatitis B and three patients with chronic severe hepatitis B,after amplification by the polymerase chain reaction.Results  (1)The mutations in CP region consisted of the double mutations(1726 A→T and 1764 G→A) and the clustering mutations(1726 A→C,1727 A→T,1730 C→G).(2)Clustering mutations in CP associated with AsC developing acute exacerbation.They were observed in eight of eleven AsC developing acute exacerbation,while five patients with chronic hepatitis B with obscure signs and four AsC had no clustering mutations in CP.Moreover,the clustering mutations were found negative in the state of AsC and positive after acute exacerbation in a subject.(3)The patients with both the clustering mutations and the double mutations manifested severe hepatitis or active cirrhosis with high level of serum HBV DNA, HBV DNA positive by dot blot,HBeAg negative and Anti  HBe positive in serum.Conclusion  The clustering mutations in CP region are associated with acute exacerbation in AsC,and co  existence of the clustering mutations and the double mutations is related to the severity of chronic hepatitis B.