DNA fragmentation induced by endonucleases is a hallmark of apoptotic process. One of the endonucleases responsible for apoptotic DNA fragmentation has been identified as DNase gamma. It has been suggested that massive nuclear debris observed in histiocytic necrotizing lymphadenitis (HNL, Kikuchi disease) results mainly from apoptosis of T-lymphocytes rather than necrosis. To identify the role of DNase gamma in apoptotic foci of HNL paraffin embedded tissue sections of HNL and lymphadenopathy with hyperplastic germinal centers and paracortex in the neck lymph nodes were immunohistochemically stained for DNase gamma and the results compared with the reactivity of TdT-mediated dUTP nick end labeling (TUNEL). Immunoreactivity for DNase gamma was detected in fragmented and condensed nuclei found abundantly in HNL as well as TUNEL reactivity. Moreover, the ratio of DNase gamma immunoreactivity to TUNEL reactivity, which represents probability of apoptosis relevant to DNase gamma, was higher in foci of nuclear debris in HNL than in the hyperplastic paracortex in lymphadenopathy including T-cell apoptosis. Our findings suggest that apoptosis detected in HNL depends more specifically upon DNase gamma than apoptosis in the hyperplastic paracortex of lymphadenopathy, and that the dysregulation of DNase gamma activation is involved in apoptosis in HNL.