Background/Aims: Deletions of the pre-S region were found in patients with chronic hepatitis and they may have an impact on the progression of chronic hepatitis B virus (HBV) infection. Thus, it is important to study deletion mutants in the pre-S region to characterize their pathogenic relevance during HBV infection. Methods: Deletion patterns of the pre-S region of HBV were analyzed in 26 patients with liver diseases (5 HBsAg-positive healthy carriers, 13 patients with chronic B hepatitis, 4 patients with liver cirrhosis, 4 patients with fulminant hepatitis). The pre-S sequence of HBV DNA extracted from sera of the 26 patients was amplified by polymerase chain reaction and sequenced directly. Results: Deletion mutants of HBV pre-S region were not observed in HBsAg-positive healthy carriers and in patients with liver cirrhosis. However, deletion mutants were detected in 7 of the 13 patients with chronic hepatitis and 2 of the 4 patients with fulminant hepatitis. Among 7 patients with chronic hepatitis who had deletions in the pre-S region of HBV, 183 bp and 150 bp deletion mutant in the distal pre-S1 region was detected in 4 patients and 1 patient, respectively. Another 30 bp deletion in the proximal pre-S2 region was detected in 2 patients. A short deletion (15 and 31 bp) in the proximal pre-S2 region was detected in 2 of the 4 patients with fulminant hepatitis. During follow-up of 3 patients, deletion was observed in 2 pateints with persistent ALT elevation. However, deletion mutant was replaced with wild-type HBV after ALT normalization in one patient. Conclusions: These findings suggest that selection occurs for the pre-S defective mutant strain of virus during severe hepatic inflammation.