The subclass distribution of antiviral antibodies to three herpes viruses was studied in a population of healthy blood donors. Subclassification by monoclonal antibodies led to the identification of certain viral IgG patterns. IgG1 appeared to be formed in response to almost all CMV, HSV-1 and VZV infections. A higher frequency of virus-specific IgG3 to CMV and HSV-1 suggested that these infections may be reactivated subclinically more often than VZV. The presence of CMV and VZV IgG4 showed a familial relationship, while IgG4 responses to HSV-1 were common. Persons with IgG4 as the only subclass-reactive antibody to CMV showed cell-related reactivities in a high frequency. Patients with leukemias, myelomas and Crohn's disease had a near-normal subclass pattern to the herpes viruses.