The 2nd-generation anti-HCV test system was applied to a Saudi Arabian multi-ethnic donor population. When donors were stratified according to first-time donations versus repeat donations, the latter having been screened previously by a 1st-generation set of tests, it was found that in Saudi Arabian and Middle East nationals, the 2nd-generation tests (EIA and RIBA), identified close to double the number of anti-HCV-positive donors, compared to an earlier study using the 1st-generation tests. Part of this finding was due to a 38% higher rate of RIBA-confirmable repeat-positive EIA results. In groups of donors, previously screened by the 1st-generation system, some additional cases of anti-HCV reactivity were identified, most prominently in Middle East nationals. It is assumed that some of these represented recent seroconversions, while others were cases of serologic subtypes of HCV, not reacting in the 1st-generation tests. The current test system identifies 0.66% of Saudi-Arabian, and 2.87% of other Middle East donors as putative carriers of hepatitis C virus. The study lends support to the opinion that donors who return regularly over the years have a lower prevalence of disease markers, thereby being a safer source of blood than first-time donors.