Elastofibromas are localized proliferations of mesenchymal cells that produce an exuberant amount of elastin-rich extracellular matrix. Recently periosteal fibroblasts have been proposed to be the proliferating cell. The hypothesis has been tested that osteocytes or osteoblasts contribute to the formation of elastofibromas by secreting a compound(s) that enhances elastin production. Media conditioned by murine calvarial osteoblasts (MC3T3) increased tropoelastin synthesis in bovine ligamentum nuchae fibroblasts. Addition of MC3T3-conditioned medium to bovine ligamentum nuchae fibroblast cultures produced a two-fold increase in tropoelastin RNA. The maximal increase in tropoelastin RNA was between 16 and 24 h; tropoelastin mRNA had returned to control values by 40 h. A similar increase in tropoelastin protein production was detected. The soluble elastogenic compound was neither interleukin-1 (IL-1) nor IL-6. These results support the hypothesis that an interaction between bone and perosteum may be involved in the formation of elastofibromas.