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In vivo implantation experiments have shown that ethylenediaminetetraaceticacid(EDTA)-soluble frac tions of dentin stimulate reparative dentinogenesis . When isolated embryonic dental papillae were cultured in the presence of these dentin constituents, odontoblast cytological and functional differentiation could be initiated and maintained in the absence of an enamel organ. These effects were attributed to the presence of TGF-/1- related molecules [TGF-/11 or bone morphogenetic protein -2a (BMP-2a)] which had to be used in combination with an EDT A-soluble fraction of dentin in order to specifically affect competent preodontoblasts . These EDT A-soluble constituents present in dentin could be replaced by heparin or fibronectin which both have been reported to interact with TGF-/1. The association of such defined matrix components with a TGF-/1-related molecule represents a biologically active complex triggering odontoblast functional differentiation. In response to caries, odontoblasts modulate their secretory activity and are stimulated to elaborate reactionary dentin. This might be induced by active molecules such as IGF, TGF-6 or BMP which are liberated from dentin consecutively to the demineralization process. Reparative dentinogenesis is distinct from reactionary dentinogenesis and more complex since it implicates the differentiation of precursor cells present in the dental papilla. The developmental history of these cells is different from that of the physiological predontoblasts in developing teeth. The nature of these "stem cells" and the mechanism of their induction still remain open questions.