The prevalence of mutations in the precore and core promoter regions of hepatitis B virus DNA and the association with the hepatitis B e antigen-negative phenotype vary in different geographical areas. It is rather high especially in the Far East and Mediterranean countries. The mutations occurring in the precore and the minimal essential region of the core promoter of HBV-DNA were analyzed in the sera of 81 patients (HBeAg-positive, 47 patients; HBeAg-negative, 34 patients) with chronic hepatitis B virus infection by direct sequencing of amplified polymerase chain reaction products. All patients had thymine at nucleotide 1858. Seven of 47 HBeAg-positive patients (15%) and 29 of 34 HBeAg-negative patients (85%) had precore stop codon mutations (G to A change at nucleotide 1896). No nucleotide change was found in the minimal essential region of HBV core promoter in any patient studied. In conclusion, the hepatitis B e antigen-negative phenotype in Turkish patients with chronic hepatitis B is associated with mutations in the precore but not in the minimal essential region of the core promoter. These results representing a part of the eastern Mediterranean support the studies conducted for the other populations of the region.