Thirty patients with chronic active Epstein-Barr virus (CAEBV) infection were analyzed. The study group included 18 male and 12 female patients, ranging in age from 5 to 31 years with a mean age of 14.2 years. Not all patients had high titers of EBV-specific antibodies, but all patients had high viral loads in their peripheral blood (more than 10(2.5) copies/microg DNA). Fifty percent of the patients displayed chromosomal aberrations, and 79% had monoclonality of EBV. Patients were divided into 2 clinically distinct groups, based on whether the predominantly infected cells in their peripheral blood were T cells or natural killer (NK) cells. Over a 68-month period of observation, 10 patients died from hepatic failure, malignant lymphoma, or other causes. Patients with T-cell CAEBV had a shorter survival time than those with NK-cell type of disease.