Interferon regulatory factors (IRFs) are multifunctional transcriptional factors. To define the role of IRFs in lymphoid disorders, we determined the expression patterns of IRF3 and IRF7 by immunohistochemistry in 5 normal lymph nodes, 12 reactive hyperplastic lymph nodes, and 27 pediatric lymphomas. IRF3 was prominently expressed in the nuclei of the histiocytes, and was expressed very weakly in the cytoplasm of most of the lymphocytes of the normal lymph nodes. However, IRF7 was expressed strongly in the nuclei of over 50% of the lymphocytes throughout the normal lymph nodes, but the histiocytes and fibroblasts were spared. In the reactive hyperplastic lymph nodes, the number of IRF3- and IRF7- positive cells in the nuclei was elevated. In the lymphomas, the number of IRF3-positive cells in the nucleus appeared to have decreased, and the cells were scattered throughout the lymphoma tissue in no specific pattern. However, in most cases the number of IRF7-positive cells was elevated. These results suggested that IRF3 was activated principally in the histiocytes and T cells under inflammatory conditions, but IRF3 activation was attenuated in cases of lymphoma. However, the number of IRF7-positive cells was found to be elevated in the reactive hyperplastic lymph nodes and pediatric lymphoma.