Laboratory diagnosis of Epstein-Barr virus (EBV) infection is based mainly on serological tests. The analysis of the pattern of class-specific immunoglobulin response against defined viral antigens, i.e. virus capsid antigen (VCA), early antigen (EA) and Epstein-Barr nuclear antigen (EBNA), permits the differentiation between primary, latent and secondary (reactivated) EBV infection. In recent months, numerous test kits for the detection of VCA specific IgM antibody have been introduced on the international market. With a panel of well defined sera, the sensitivity and specificity of eleven different commercially available IgM ELISAs was evaluated. A well established, commercially available, indirect immunofluorescence assay (IFA) served as the reference test. Compared to the IFA, the Biotest and Sigma Diagnostic assays had the highest sensitivity for the detection of IgM antibody to VCA or EA. A variable number of false positive results (n = 0-9) was obtained with the EBV-IgM assays by testing potentially cross-reactive serum samples. Up to 19 serum samples from immunocompromised organ transplant recipients were found positive with the Sigma Diagnostics assay. The results of this study show that there are great differences in quality of current EBV-IgM-ELISA test kits. Depending on the clinical setting, it may be important to use a test kit which detects immunoglobulin M reactivity to EA in order to warrant an optimal sensitivity for the serological diagnosis of EBV reactivation in immunocompromised patients. However, since most immunosuppressed patients have serological reactivations, and in most cases these are asymptomatic, the clinical relevance of the detection of EA-IgM is very low.