Experimental caries was induced in rats that were inoculated orally with Streptococcus mutants and maintained on a cariogenic diet. During the caries process, kinetics of the pulpal la antigen-expressing cells and macrophages was monitored immunohistochemically and was correlated with caries depth and the status of reparative dentin formation. Initial pulpal response was characterized by a localized accumulation of la antigen-expressing cells beneath the dentinal tubules communicating with the superficial caries. This was followed by a caries-depth related increase of la antigen-expressing cells and macrophages in the coronal pulp. The accumulation of these cells under the dentin was most apparent when the caries had progressed into the reparative dentin. These findings suggest that the response of la antigen-expressing cells to carious irritants triggers the defense reactions of the pulp. The intensity of the defense reactions may be correlated with the permeability of carious dentin.