Recombinant human bone morphogenetic protein (BMP)-2, BMP-4 and transforming growth factor (TGF)-beta 1 combined with collagen matrix as a carrier were examined for their effects on pulp regeneration and dentine formation. Seventy days after implantation of 2 micrograms of BMP-2, mineralized osteodentine-like tissue containing embedded osteodentinocytes was seen in the cavity. Unmineralized fibrous tissue and pulp-like loose connective tissue were also found in the same cavity. In teeth implanted with 660 ng of BMP-2 only unmineralized fibrous and pulp tissues were seen. In teeth with 220 ng of BMP-2 or collagen alone, pulp tissue was seen. It is therefore likely that the cavity fills with pulp tissue and that spindle-shaped cells elaborate extracellular matrix that mineralizes to be osteodentine in a dose-dependent manner. Similar osteodentine was seen in teeth implanted with 4 micrograms of BMP-4 and collagen. No distinct tubular dentine was formed, unlike an earlier experiment in which BMP-2 or -4 was implanted with enriched, inactivated dentine matrix. These findings suggest that both BMP-2 and -4 induce osteodentine formation if combined with collagen matrix; some other matrix component present in inactivated dentine matrix might be essential for further differentiation into odontoblasts. In teeth implanted with TGF-beta 1, the carrier collagen remained in the cavity and little pulp tissue proliferation was seen, suggesting a possible inhibitory effect of TGF-beta 1 in pulp regeneration. It is likely that the response to growth and differentiation factors is dependent on the state of differentiation of pulp cells.