The molecular specificity of the antibody response against Epstein-Barr Virus (EBV) is studied in patients with acute primary EBV-infection, i.e. infectious mononucleosis syndrome. Using the immunoblot technique both IgM and IgG antibody responses are studied in sera obtained serially until week 20 after onset of symptoms. Healthy seropositive blood donors are used as control. Antigens are prepared from virus producer cell lines B95-8, P3HR1 and HH514-c16 (a superinducible derivative of P3HR1), induced for the expression of early antigens (EA) or viral capsid antigens (VCA) and from the EBV-negative cell lines BJAB and RAMOS. The 'WC'-serum, described by Edson et al. (J. Immunol. 130, 1983) is used to characterize EA- and VCA-specific polypeptides and to define their subcellular location. The immunoblot studies reveal an enormous diversity in EBV-specific polypeptides recognised by different individual patients, both for IgM and IgG. In addition, these patterns were markedly different from those found with control blood donor sera. The latter predominantly recognised bands at 72 kDa (EBNA) and 41 and 18 kDa respectively (both VCA components). Despite the great individual variation observed, EA-specific polypeptides at 138 kDa and at 45-52 kDa were recognised by both IgM and IgG antibodies in first serum samples of all patients tested.