Isolation of HCV replicon cell lines possessing IFN-resistant phenotype. Three stable replicon cell lines (Con-24, Con-17 and Con-15) having low ISRE-promoter activation and three replicon cell lines (9/13, 5/15 and KR) with high ISRE promoter activation were treated with or without interferon alpha 2b (1000 IU/ml) for 4 weeks in a growth medium containing G-418 (1 mg/ml). The ability of replicon cells to develop G-418 resistant cell colonies was examined. Cell colonies were developed only in low ISRE replicons. Three individual colonies from each dish were picked up and nine stable cell lines were generated.