In order to better understand the features of chronic active Epstein-Barr (EB) virus infection, we employed two-colour immunofluorescence staining with monoclonal antibodies and flow cytometry analysis to study the lymphocyte phenotypes of two patients with severe symptoms of this disorder as well as four patients with mild symptoms. We found an increased number of activated T cells, as characterized by CD4+Ia+, CD8+Ia+, or CD4+Tac+ phenotypes, and a markedly decreased CD4+2H4+ T cell subpopulation, previously characterized as a suppressor-inducer subset, in the patients with severe symptoms. In contrast, the four patients with mild symptoms showed only a slightly elevated number of activated T cells and a normal CD4+2H4+/CD4+ ratio. These phenotypic differences may suggest heterogeneity in this disorder. Also, a failure in the suppressor-inducer population could contribute to changes in the host-virus relationship and the degree of the decrease in this population may correlate directly with the severity of the disease.