We report here that transforming growth factor-beta (TGF-beta) can increase the expression level of macrophage colony-stimulating factor (M-CSF) mRNA in a variety of mesenchymal cell lines derived from osteoblasts, bone marrow stromal cells, fibroblasts, and myoblasts. The M-CSF activity in the conditioned medium of mouse osteoblast-like MC3T3-E1 cells was increased by TGF-beta as well as interleukin-1 (IL-1) treatment. The increase of M-CSF mRNA expression was observed as early as 2 h after TGF-beta or IL-1 addition and was superinduced by cycloheximide treatment. Nuclear run-off assays revealed that the increase in M-CSF mRNA by TGF-beta as well as IL-1 occurred, at least in part, at the transcriptional level. Platelet-derived growth factor (PDGF) also enhanced the M-CSF production in MC3T3-E1 cells. Furthermore, TGF-beta and IL-1 distinctly induced both PDGF-A and PDGF-B chain mRNA in MC3T3-E1 with different time courses. Our present studies suggest that PDGF autocrine loop-dependent and loop-independent pathways could modulate the M-CSF production stimulated by TGF-beta or IL-1 and account for the complexity of the cytokine network involving M-CSF in vivo under various physiological and pathological conditions.