For the serological diagnosis of Herpesvirus infection, increasing use is made of the determination of the antibodies against virus-specific early antigens. The presence of serum antibody to early antigens is a widely accepted marker of acute Epstein-Barr virus infection or Varicella-Zoster virus infection. Controversial data are present in the literature about the significance of Cytomegalovirus early antigens antibody response. This is discussed in view of the possibility that controversial results could be due to different methods used to produce early antigens by different authors.