Twenty-one patients undergoing endodontic surgery were identified. Periradicular tissue samples were recovered, and those showing significant numbers of polymorphonuclear leukocyte (PMN) infiltration were prepared for immunoperoxidase identification of interleukin (IL)-1 alpha and IL-1 beta-producing cells using specific polyclonal antibodies. In selected tissue specimens, 90% or more of the PMN's were found to stain positively for IL-1 alpha and IL-1 beta. In addition, significant numbers of plasma cells and tissue histiocytes stained positively for these IL's. Cell suspensions from selected periapical granuloma specimens, as well as from purified peripheral blood PMN's and peripheral blood mononuclear cells, were also subjected to IL-1 quantitation using a commercial ELISA procedure. Such cell suspensions were found to produce significant levels of IL and could be stimulated to produce increased levels after coculture with lipopolysaccharide. These results suggest that PMN's in inflammatory periradicular tissues may be a significant source of IL-1, and their possible roles in the establishment and resolution of periradicular lesions need to be re-evaluated.