The aim of this study was to explore the prevalence of basal core promoter (BCP) and precore gene (PC) mutations in hepatitis B virus (HBV) isolates among the Nicobarese tribe and their relationship with genotypes and HBeAg status. A total of 726 blood samples were collected from two villages of the Car Nicobar Island where mass vaccination was performed in the year 2000. HBV DNA was isolated and the BCP and PC regions were amplified and sequenced directly. The samples positive for HBV DNA were tested for HBsAg, HBeAg and anti-HBe. Among the 211 and 515 samples collected from vaccinated and nonvaccinated persons, 16 and 82 were positive for HBV DNA, respectively. Among the vaccinated individuals, only 1 had a mutation in both the BCP and PC gene. Among the nonvaccinated subjects, 3 (4.5%) had an A1762T mutation, 8 (12.1%) had a G1764A mutation, 11 (16.7%) had a G1896A mutation and 4 (6.1%) had a G1899A mutation. The HBeAg-negative subjects had a significantly higher frequency of BCP and PC mutations than the HBeAg-positive subjects. The prevalence of a PC mutation was higher than that of a BCP mutation. The present study stresses the need for the continuous surveillance of subjects with BCP and PC mutations, as the mutations may contribute to the progression of liver disease.