561 out of 2,777,021 blood donations from 582,655 donors tested confirmed positive for anti-HCV (RIBA II or Matrix Dot), 549 of them at their first donation, in their first HCV test ever, or in the first HCV test with a new, more sensitive test generation. Thus, our anti-HCV prevalence is 0.037% or 1 in 2,679 donations; among first-time donations it is five times higher than among repeat donations. Twelve repeat donors seroconverted, yielding an anti-HCV incidence of 0.0008% or 1 in 122,570 repeat donations and a seroconversion rate of 2.32 per 10(5) repeat donor person-years. The residual risk associated with transfusion of blood for repeat donors amounts to 5.2 per 10(6) repeat donations. We estimate a risk reduction from introduction of direct virus genome testing after PCR to be at 3.7 per 10(6) repeat donations. Look-backs among recipients of the last seronegative blood products from 12 donors with subsequent seroconversion revealed no recipient infection. Thus, today the residual risk for HCV transmission through transfusion of blood components obtained from Lower Saxony blood donors is quite low. The added safety from direct virus genome testing after PCR is considered extremely low, which casts doubt on the cost-effectiveness of such a measure.