To investigate the relationship of the HBV C gene mutations with the disease progress, the hotpoint mutations of pre- C stop28 and C region L97 were examined with restrictio-fragment-length-polymorphism (RFLP) technique in 91 hepatitis patients with diverse clinical features and HBe status. Both mutations were almost not seen in acute hepatitis B and chronic asymptomatic virus carriers; rarely in chronic persistent hepatitis and frequently in chronic active hepatitis (CAH) and active liver cirrhosis (ALC), accounting for 80% and 78% in CAH and ALC respectively. The pre-C mutant was mixed with wild strain in 11 of 31 patients who were HBeAg-positive CAH and ALC; on the other hand, the wild strain also coexisted with variant in anti-HBe-positive cases. So did the L97 in both HBeAg- and anti- HBe-positive cases. Possibly, both the mutant and the wild strain are usually in a relatively growth and decline status. So, the hot-point mutations of HBV C gene were closely related with the disease activity.