Context. - Kikuchi disease is a self-limiting febrile lymphadenopathy characterized by a patchy area of apoptosis. Kikuchi disease is thought to be caused by a virus, but this has not been clearly demonstrated. Human herpesviruses 6 and 7 (HHV-6 and HHV-7) are lymphotropic viruses that can induce apoptosis in infected lymphocytes. Recently, HHV-8 was reported to be a possible etiologic agent of Kikuchi disease. Objective. - To investigate the incidence of HHV-6, HHV-7, and HHV-8 infection in patients with Kikuchi disease. Design. - Seventy archival tissue specimens (from 50 Kikuchi disease cases and 20 control cases) were tested for the presence of HHV-6 and HHV-7 using a nested polymerase chain reaction, and for the presence of HHV-8 using single-step polymerase chain reaction. Immunohistochemistry for HHV-8 expression was carried out in those cases in which HHV-8 was detected using polymerase chain reaction. Results. - Of the 50 cases with Kikuchi disease, 21 (42%) were HHV-6 positive and 32 (64%) were HHV-7 positive. Eight (40%) of the 20 control cases were HHV-6 positive and 9 (45%) were HHV-7 positive. Both HHV-6 and HHV-7 were detected in 15 (30%) of the cases with Kikuchi disease and in 3 (15%) of the control cases. Three (6%) of the 50 cases of Kikuchi disease were HHV-8 positive but revealed no positive cells on immunohistochemical analysis for HHV-8. Human herpesvirus 8 was not expressed in any of the control cases. Conclusions. - There was no association between the presence of HHV-6 or HHV-7 and Kikuchi disease. Because the HHV-8 genome but not protein was detected in a small proportion of the cases of Kikuchi disease, its potential causative role in this disease should be determined by further studies.