This article revisits the induction of bone by the osteogenic proteins of the transforming growth factor-beta superfamily in nonhuman and human primates and proposes that the translation in clinical contexts of the phenomenon of bone; formation by autoinduction, is predictably achievable by the binary application of relatively low doses of transforming growth factor-beta proteins with a recombinant human osteogenic protein. The synergistic induction of bone formation is a cost-effective clinical strategy because published data in nonhuman primates have shown that doses of recombinant human recombinant osteogenic protein-1 can be reduced at least fivefold and still increase bone formation compared with higher doses of single applications of human recombinant osteogenic protein-1.