The hepatitis C virus (HCV) F protein is a recently described, frameshift prod uct of HCVcore encoding sequence of genotype 1a. Its function and antigenic prop erties are unknown. Using enzyme-linked immunosorbent assay, we assessed the pr evalence of anti-F antibodies in 154 patients chronically infected with HCV, 65 patients with other liver diseases, and 121 healthy controls. For this purpose, we expressed a highly purified HCV F recombinant protein from HCV genotype 1a i n Escherichia coli. Because the F protein shares the 10 first amino acids with the core protein, the anti-HCV F response was also assessed by a F recombinant p rotein deleted of its 10 first amino acids <<(1-10)F>>. Ninety-six (62%) of the 154 HCV serum samples reacted with the complete F recombinant protein, whereas 39 (25%) showed a weaker anti-(1-10)F reactivity and 150 (97%) had anti-core antibodies. No reactivity against F, (1-10)F, or core was detected in any of the controls. To exclude a potential cr oss-reaction of anti-F antibodies with anti-core antibodies, a specific enzym e-linked immunosorbent assay was performed for anti-core antibodies. The speci ficity of anti-F antibodies was confirmed using an F synthetic peptide. The pre valence of anti-F antibodies did not correlate with HCV RNA serum level, genoty pe, or stage of liver disease. Sequence analysis from 8 anti-F-positive and 5 anti-F-negative serum samples did not reveal any particular difference potenti ally accounting for their respective anti-F responses. In conclusion, the F pro tein elicits specific antibodies in 62%of individuals chronically infected with HCV; such anti-F response does not seem to be affected by the F sequence heter ogeneity. Its function and antigenic prop erties are unknown. Using enzyme-linked immunosorbent assay, we assessed the pr evalence of anti-F antibodies in 154 patients chronically infected with HCV, 65 patients with other liver diseases, and 121 healthy controls. For this purpose, we expressed a highly purified HCV F recombinant protein from HCV genotype 1a in Escherichia coli. amino acids with the core protein, the anti-HCV F response was also assessed by a F recombinant p rotein deleted of its 10 first amino acids << (1-10) F >>. Ninety-six (62%) of the 154 No reactivity against F, (1-10%) had anti-core antibodies reacted with F (1-10% ) F, or core was detected in any of the controls. To exclude a potential cr oss-rea The speci fi c of anti-F antibodies was identified as anti-core antibodies, a specific enzym e-linked immunosorbent assay was performed for anti-core antibodies. The pre valence of anti- F antibodies did not correlate with HCV RNA serum level, genoty pe, or stage of liver disease. Sequence analysis from 8 anti-F-positive and 5 anti-F-negative serum samples did not reveal any particular difference potenti ally accounting for their respective anti-F responses. In conclusion, the F pro tein elicits specific antibodies in 62% of individuals chronically infected with HCV; such anti-F responses does not seem to be affected by the F sequence heteroegeneity.