The diagnosis of acute cytomegalovirus (CMV) infection is frequently based on a positive IgM result. False-positive reactions due to interfering infections may exist. Between August 1998 and May 1999, 62 patients were found to be IgM positive and IgG negative with the Axsym assay (Abbott, Germany). Serological testing for Epstein-Barr virus (EBV) was performed in these patients to detect any cross-reactivity due to acute mononucleosis. Additionally, the results of the CMV Axsym was evaluated in 40 patients with acute EBV infection. The results suggest that the CMV-IgM Axsym assay shows a lack of specificity due to acute EBV infection. Precautions must be taken when CMV-IgM Axsym results are interpreted. It seems necessary to confirm equivocal results with another technique and to take into account other clinical and biological observations.