Blood donations collected in Scotland are currently screened for the presence of HBsAg, anti-HIV 1 + 2, anti-HCV and syphilis antibodies. Approximately 1% of all donations are found to repeatedly react to one of these four markers on screening but very few represent true infection. These samples must be sent to the designated confirmatory laboratory whose main role is to identify the true positive amongst a sea of 'false positives'. A battery of tests is used for this purpose, usually applied in a defined sequence. The use of such 'confirmatory algorithms' for each marker has been developed by most countries over the years and is now essential to the confirmatory process. The advent of gene amplification techniques such as PCR for initially pooled and eventually single donation testing will be the next challenge for confirmatory laboratories and will demand standards of confirmation as accurate as currently performed with the present serological markers.