Kikuchi's disease is a fairly common self-limited disorder among Orientals that usually involves the cervical lymph nodes of young individuals and occurs predominantly in females. Frequently, the disease is associated with fever or flu-like symptoms, an elevated erythrocyte sedimentation rate (ESR), neutropenia, and lymphocytosis with atypical lymphocytes in the peripheral blood, suggesting a viral origin. However, no infectious agent has been identified. The presence of Kaposi sarcoma-associated herpesvirus, known as human herpesvirus 8 (KSHV/HHV 8), was investigated by polymerase chain reaction (PCR) in archival tissue from 26 cases of Kikuchi's disease using published sequences of KSHV/HHV 8 as primers. PCR products were further characterized by Southern blot analysis. Forty reactive lymph nodes and a case of Kaposi sarcoma (KS) were included as negative and positive controls, respectively. Patients consisted of 10 men and 16 women with a mean age of 27 years. All patients were previously healthy and presented with cervical or axillary lymphadenopathy. None were positive for human immunodeficiency virus (HIV) or otherwise immunocompromised. Viral DNA was amplified by PCR in six cases of Kikuchi's disease (23%) and the control KS tissue. Southern blot analysis confirmed that the amplified products were KSHV/HHV 8. In the reactive lymph nodes, no viral genome was amplified by PCR. The presence of DNA sequences of KSHV/HHV 8 in a substantial portion of Kikuchi's disease suggests that KSHV/HHV 8 might play an important role in the pathogenesis of a subset of Kikuchi's disease.