T-helper and B-lymphocytes may contribute to mechanisms that result in bone-resorptive cytokine production in periapical lesions. Mice with severe combined immunodeficiency (seid) lack functional B- and T-cell immunity. The purpose of this study was to investigate the progression of pulp necrosis and the histomorphometric features of periapical lesions in seid vs. normal mice. The expression of the bone-resorptive cytokines IL-loe and TNF-α was also investigated. Sixteen five-week-old homozygous seid mice and 14 normal BALB/cJ mice were used. The pulps of mandibular first molars were exposed for 1, 2,3, or 4 weeks. Blocks of tissue containing the mandibular teeth and supporting structures were processed for both light microscopic examination and immunohistochemical staining for IL-1α and TNF-α. Central sections were randomized, their images were blindly digitized into a computer, and the areas of the lesions surrounding the distal root apices were measured. The cells that stained positively for the cytokines in the same area of adjacent sections were counted. Pulp necrosis progressed at similar rates in teeth from both strains. A progressive and significant increase in the periapical lesion size in both strains was observed. The seid mice lesions were significantly smaller than the controls at only the threeweek period. There was heavy cytokine staining in periapical lesions from both strains, especially in areas that contained a mixed inflammatory infiltrate or fibroblasts. The number of positively staining cells was proportional to the lesion size. Therefore, pulpal and periapical pathosis were independent of the presence of functional T- and B-cells in this model.