During an outbreak of parvovirus B19 we collected serum samples from 68 nonpregnant patients in the region of Antwerp (Belgium). Fifty-seven (84%) of the parvovirus B19 immunoglobulin M (IgM)-positive sera had a positive result for Epstein-Barr virus (EBV) IgM by Liaison testing, 61 (90%) had a positive result for herpes simplex virus (HSV) IgM, 20 (29%) samples were positive for cytomegalovirus IgM, and 15 (22%) had a positive result for Borrelia burgdorferi sensu lato IgM. As assay interference was suspected, sera were further investigated by using additional infectious-disease serology tests and by performing various interference elimination procedures. We could show that the EBV IgM and HSV IgM results were false positives due to aspecific IgM reactions with the solid phase. All samples were also analyzed by a modified Liaison EBV IgM assay, based on the addition of polyvinylpyrrolidone and polyvinyl alcohol to the dilution buffer, which partially eliminated this type of assay interference. Although the Liaison is a very convenient, automated immunoassay platform, this study demonstrates the potential for improvement of mainly the EBV IgM and HSV IgM tests.