To evaluate the effects of bioactive molecules in pulpal wound healing, we carried out experiments using the rat upper molars as an in vivo model. Cavities were prepared on the mesial aspect, and pulp perforation was accomplished by the application of pressure with the tip of a steel probe. After the pulp-capping procedure, the cavities were filled with a glass-ionomer cement. Comparison was made between and among: (1) sham-operated controls with dentin and predentin fragments implanted in the pulp during perforation after 8, 14, and 28 days; (2) carrier without bioactive substance; (3) calcium hydroxide; (4) Bone Sialoprotein (BSP); (5) different concentrations of Bone Morphogenetic Protein-7 (BMP-7), also termed Osteogenic Protein-1 (OP-1); and (6) N-Acetyl Cysteine (NAC), an anti-oxidant agent preventing glutathione depletion. Histologic and morphometric comparison, carried out among the first 4 groups on demineralized tissue sections, indicated that, at 28 days after implantation, BSP was the most efficient bioactive molecule, inducing homogeneous and well-mineralized reparative dentin. BMP-7 gave reparative dentin of the osteodentin type in the coronal part of the pulp, and generated the formation of a homogeneous mineralized structure in the root canal. These findings indicate that the crown and radicular parts of the pulp bear their own specificity. Both BSP and BMP-7 were superior to calcium hydroxide in their mineralization-inducing properties, and displayed larger areas of mineralization containing fewer pulp tissue inclusions. The overall mineralization process to these molecules appeared to proceed by mechanisms that involved the recruitment of cells which differentiate into osteoblast-like cells, producing a mineralizing extracellular matrix. We also provide preliminary evidence that NAC induces reparative dentin formation in the rat molar model. Pulp-capping with bioactive molecules provides new prospects for dental therapy.