Periapical granulomas contain a large number of T lymphocytes and monocytes/macrophages and a small number of B lymphocytes and polymorphonuclear leukocytes. Sections from eight periapical granulomas were stained by a variety of immunohistochemical methods. The vascular endothelial cells stained positively for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Helper T cells were identified by immunostaining for CD4 and stained positively for interferon-γ (IFN-γ). However, CD4-positive T cells did not stain for interleukin-4 (IL-4). Monocytes/macrophages were identified by immunostaining for CD68 and stained positively for IL-1α or inducible nitric oxide synthase (iNOS). IL-1β could not be detected in the same samples. No cytokine expression was observed in B cells identified by immunostaining for CD20. IFN-γ- and iNOS-positive cells could not be detected in clinically healthy periodontal ligament being used as a negative control. These results suggest that the IFN-γ-producing T cells and iNOS-positive cells may modulate the progress of disease in local inflammation sites such as in periapical granulomas.