We previously reported the isolation of the cartilage-derived growth promoting factors chondromodulin-I (ChM-I) and chondromodulin-II (ChM-II) from fetal bovine epiphyseal cartilage. Both of these factors stimulate the growth and matrix formation of chondrocytes in vitro. In the present study, we found that ChM-I and ChM-II stimulated the proliferation of clonal mouse osteoblastic MC3T3-E1 cells as well as primary mouse osteoblasts in culture. Unlike other known growth factors, these factors did not support the proliferation of fibroblasts. Concomitantly with growth stimulation of osteoblasts, there was a reduction of alkaline phosphatase (ALP) activity in the cells, the expression of the differentiated phenotype. These results suggest that epiphyseal cartilage may play a functional role in longitudinal bone growth by production of these unique growth-promoting factors.