- summary To examine the accuracy, feasibility and benefits of screening for hepatitis C virus core antigen (HCVAg) using enzyme-linked immunosorbent assay (ELISA) test in pools. Many countries cannot afford to test blood donations for hepatitis C using molecular methods. Screening individual units using the ELISA HCVAg test is an acceptable, yet still expensive, alternative, especially for small blood bank settings. This study evaluated the option of screening for HCVAg in pools. The sensitivity (Se) and specificity (Sp) of HCVAg in pools of three and six antibody-negative samples were estimated and compared with polymerase chain reaction (PCR). The feasibility and cost–benefit of the assay was assessed on 960 routine samples collected at a hospital blood bank in Gaza. Based on results for 50 PCR-positive pools and 50 and 110 PCR-negative pools of three and six, the Se of testing in pools of three and six samples is 80–82% [95% confidence interval (CI): 66·3–91·4] and Sp ≥98% (95% CI: 89·4–100·0) compared with PCR. The incidence of antigen in donors in Gaza was 0·1% (95% CI: 0–0·56). Cost analyses suggested significant benefits from implementing screening blood donations for HCVAg when the incidence rate is >4·2/10 000, leading to reduction in the expenditures needed to treat patients infected with HCV. The risk of transfusion-transmitted hepatitis C in resource-deprived developing countries can be efficiently reduced by additional screening of antibody-negative blood donations for HCVAg in pools of six.