One hundred ninety seven successive sera, positive for anti-hepatitis C virus antibody with a third generation screening enzyme immunoassay (MEIA on IMX, Abbott), were tested with alternative third generation screening assays from two different manufacturers (Sanofi and Ortho), with an immunoblot assay (RIBA 3.0, Chiron), and by reverse transcriptase polymerase chain reaction (RT-PCR). Samples positive by RIBA 3.0 or by RT-PCR were considered as true positives. The positive predictive value of a combination of strong positive results in two screening assays was more than 98%. This combination of results has the same predictive value for detectable viraemia as a positive RIBA 3.0 (86.5%). Using a policy of two successive enzyme immunoassays in this clinical diagnostic setting diminishes the need for supplemental assays by more than 85%.