Quantitative phenotypical analysis for macrophages and lymphoid cells was made on periapical lesions induced by making unsealed pulp exposures in rat molars. Exudative macrophages of diverse morphology were the most dominating immunocompetent cells during all experimental periods. They exhibited almost complete distribution through the periapical lesions by the onset of active lesion expansion, and their kinetics and morphology were considerably similar to Ia+ non-lymphoid cells. Lymphoid cells started to show a notable increase shortly before the onset of active lesion expansion. CD4+ lymphocytes dominated at first, whereas CD8+ lymphocytes and plasma cells were dominant when the lesion size was stabilized. These findings suggest that macrophages of heterogenous populations play essential roles in the lesion pathogenesis by acting, depending on their functional heterogeneity, as effector cells or as antigen-presenting cells that stimulate CD4+ lymphocytes to induce an immune response. Interactions between plasma cells and CD8+ lymphocytes may be related to lesion chronicity.