Bone formation is a process regulated by effects on bone cell replication and on differentiated function, which is primarily represented by changes in bone collagen synthesis. The effects of hormones on bone formation have been reviewed extensively, and this article describes the effects of systemic and local growth factors. Systemic growth factors, such as epidermal growth factor and fibroblast growth factor, stimulate cell replication in skeletal and nonskeletal tissues but inhibit differentiated function; platelet-derived growth factor stimulates cell replication and generalized protein synthesis by differentiated cells. The only systemic factor that simultaneously stimulates bone cell replication and differentiation is insulinlike growth factor, or somatomedin. The growth of skeletal and nonskeletal tissues also appears to be regulated by locally synthesized factors. Bone contains an autologous bone-derived growth factor that stimulates bone collagen and DNA synthesis, while cartilage contains a somatomedinlike peptide that stimulates cartilage growth. Other noncollagenous bone proteins, such as osteonectin and osteocalcin, might have a role in mineralization, but, as yet, they have not been reported to have a definite effect on bone formation. Bone also contains prostaglandins and local regulators of bone resorption, while the macrophage, an osteoclast-related cell, releases peptides that stimulate bone formation in vitro. In conclusion, bone formation is a complex process regulated not only by hormones but also by systemic and local growth factors.