BACKGROUND: Screening of blood donors for markers of transfusion-transmissible infectious agents leads to a varying number of false-reactive test results and sometimes thereby temporary or permanent deferral of donors and also to loss of collected units. STUDY DESIGN AND METHODS: Data on false-reactive screening test results in 2002 and 2003 were collected from 19 blood centers in Sweden. A questionnaire was sent to donors deferred because of false-reactive screening test results to investigate their perception of the information and their reaction to the deferral. RESULTS: Testing of 21,189 samples from new donors and 423,543 donations from regular and/or repeat donors produced 1,059 false-reactive test results, mostly from hepatitis C virus antibody testing, and 299 deferrals. Six different human immunodeficiency virus tests led to between 0.02 and 0.2 percent false-reactive results. The deferral rate varied considerably between different counties. Of 204 deferred donors contacted, 180 (88%) answered the questionnaire. More than 80 percent were worried about their test results and worry was more common among those who did not feel sufficiently informed. CONCLUSION: The results imply that there is a need for a more standardized approach to the screening of blood donors and donations with the aim of minimizing the number of false-reactive screening test results. They also emphasize the importance of appropriate information and support to deferred donors.