BACKGROUND: E2/nonstructural protein 1 (E2/NSl) glycoprotein of hepatitic C virus (HCV) is most variable region of HCV and appears to cause positive selection of escape mutants, which may play a role in the mechanism of persistent viral infection. We analyzed the sequence diversity of E2/NSl of HCV from twelve Koreans. METHODS: The nucleotide and deduced amino acid sequences of the putative E2/NSl region of HCV were determined by analysis of twelve independent amplified CDNA clones obtained from Korean patients with chronic hepatitis and primary hepatocellular carcinoma, using dideoxynucleotide chain termination method. RESULTS: High level of variations in both nucleotide and amino acid sequences were observed in the hypervariable region 1 and 2 (HVR1 and HVR2). Sequences of HVR1, situated at the nucleotide positions from 1478 to 1552 (amino acid positions : from 383 to 407), showed from 27.8 to 94.4% diversity at the nucleotide level and from 25.0 to 87.5% diversity at the amino acid level. 4 few amino acid residues (amino acid positions: 384, 388, 389 405, 406) within HVR1 were highly conserved in most cases. Sequences of HVR2, situated at the nucleotide positions from 1736 to 1774 (amino acid positions from 469 to 481). Two groups of highly conserved amino acid sequences were observed in the HVR2 of twelve Korean cases, indicating that there are type specific conservation in the HVR2 region. 4 large part of the eave lope region located at the nucleotide positions from 1832 to 1892 (amino acid positions : from 501 to 521) was highly conserved, to show 100% Identity of amino acid sequences. The positions of six putative N-glycosylation sites were highly conserved. The percent diversities of nucleotide of E2/NSl was from 60.4% to 92.7% and the percent diversities of amino acid of E2/NSl was from 57.6% to 95.5% among twelve Korean HCV clones. CONCLUSION: Extensive genetic variations including two hypervariable regions were clustered and interspersed with highly conserved nucleotides sequences in E2/NSl region of HCV isolated from Koreans.