In order to elucidate the possibility of lymphoproliferation in cases of chronic active Epstein-Barr virus infection (CAEBV), to clarify the clonality and genotype of proliferating lymphocytes, and to search for the factors that induce lymphoproliferation, we studied 11 cases of CAEBV, using genetical and immunological techniques. Epstein-Barr virus (EBV) DNA in peripheral mononuclear cells was detected in eight cases by Southern blotting. Among those eight cases, monoclonal proliferation of EBV DNA-positive cells was observed in three cases and oligoclonal proliferation in three cases. In the cases of monoclonal proliferation, one case manifested T-cell lymphoproliferation and the rest natural killer (NK) cell lymphoproliferation. The anti-EBV antibody titers in the study did not have any relativity to lymphoproliferation. On the other hand, three of the four cases of NK cell lymphoproliferation and one of the two cases of T-cell lymphoproliferation exhibited hypersensitivity to mosquito bites (HMB) in their clinical histories, while none of the three nonlymphoproliferation cases did. These facts indicate that T-cell and NK cell lymphoproliferative diseases (LPDs) could be more closely associated with EBV infection than we had previously expected. Also, the anti-EBV antibody titers may not be the indicator of EBV-associated LPD, and HMB may be one of the factors that induce EBV-associated LPD.