Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) is a well defined disorder primarily affecting young adults. The cause of this disease is still unknown. The authors report a case of a 37-yar old woman with Kikuchi-Fujimoto disease and systemic lupus erythematosus (SLE). Serologic testing for HHV-6 antibodies revealed an active infection. An excised cervical lymph node contained HHV-6 genome demonstrated by using in situ hybridization. Active HHV-6 infection should be considered in Kikuchi-Fujimoto disease.