Transforming growth factor beta (TGF-beta) was tested for its ability to stimulate a chemotactic response in Stage 24 embryonic chick limb bud mesenchymal cells and muscle-derived fibroblasts. TGF-beta stimulated dose-dependent chemotaxis in both cell populations. Maximal chemotaxis was achieved with a concentration of 5 ng/ml for limb bud cells and as low as 15 pg/ml for muscle-derived fibroblasts. TGF-beta was not chemokinetic at these levels. Several other proteins found in bone, namely fibronectin, type I collagen, and osteonectin, were not chemotactic. However, both Bone Gla-protein and basic-FGF were found to be chemotactic but less effective than TGF-beta. Comparison with extracts of adult bone indicates that while TGF-beta is a potent chemoattractant, it does not account for all the chemotactic activity found in adult bone.