Epstein-Barr virus (EBV)-specific antibody titers were investigated in 60 patients with ataxia-telangiectasia (AT) and 22 healthy members of their families. In addition, we studied 36 patients with primary immunodeficiencies, Behçet disease, and other conditions and 61 unrelated healthy controls. Twenty-seven AT patients were examined sequentially at intervals varying from 2 months to 8 years. The AT patients showed an increased incidence (66.6%) of high antibody titers (greater than or equal to 1:320) to viral capsid antigen (VCA) and also a high incidence (35%) of antibody titers to early antigens (EA), but low titers (less than 1:10) of antibodies to the EBV-associated nuclear antigen (EBNA) in 35% of the patients. The geometric mean titers (GMT) of antibodies to VCA were five to six times higher; those of anti-EBNA were five times lower in AT patients as compared with control groups. In serial determinations, anti-VCA and anti-EBNA titers remained constant with the exceptions of two patients who developed ALL and Hodgkin lymphoma. The patients with other diseases did not differ significantly from the controls, with the exception of lower titers (less than 1:10) of anti-EBNA (52.8%). AT patients with low anti-EBNA titers tended to have more advanced T-cell deficiencies than those with moderate anti-EBNA titers, as detected by total lymphocyte and E-rosetting cell counts and skin test responses. The percentage of patients with low serum IgA levels was found to be higher in the low anti-EBNA group than in the moderate anti-EBNA group (44.5 vs 20%).