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A licensed recombinant immunoblot assay (RIBA) has been an integral component of the algorithm for confirmation of reactivity for antibody to hepatitis C virus in screening assays. This test may become unavailable in the future, so we have investigated the potential value of screening test signal values to support confirmation. Depending on the screening test used (Ortho enzyme-linked immunosorbent assay or Abbott PRISM chemiluminescent assay), signal-to-cutoff ratios of 5.00 and 3.20, respectively, were shown to have positive predictive values of 89.1 and 95%, with sensitivities of 93.1 and 88.7% relative to RIBA. However, additional steps will have to be added to assure equivalent performance to RIBA.