Screening of linear epitopes within the hepatitis C virus (HCV) E1/E2 region for their ability to induce natural killer‐mediated antibody‐dependent cellular cytotoxicity (NK‐ADCC). Individual synthetic HCV‐E1E2 peptides were precoated onto 96‐well plates and incubated with serum samples from five different chronic HCV carriers (genotype 1b for 37 and 121; genotype 2a for 204, 152 and 271). Purified NK cells from two healthy donors (donor A for the upper panel and donor B for the lower panel) were used as effector cells. Interferon (IFN)‐γ levels in cell‐free supernatants were determined by enzyme‐linked immunosorbent assay (ELISA). HCV patient no. 271 was not tested with donor B NK cells due to the limited amount of serum available. Peptides 3, 6, 11, 14 and 17 (indicated by black dots) induced higher NK‐ADCC responses than the other 12 peptides in both donors. Six putative neutralizing epitopes overlapped with peptides 1, 5, 7, 8, 10 and 12 are indicated by pink columns. The median and the interquartile ranges are shown for each peptide. [Colour figure can be viewed at wileyonlinelibrary.com].