Transforming growth factor-beta (TGF-beta) autoregulates its expression in several mammalian cell types. We now report that addition of TGF-beta-s 1, 2, and 3 to primary chicken embryo cells differentially affects expression of the messenger RNAs for the different TGF-beta isoforms depending on the cell type. In cultured sternal chondrocytes, addition of TGF-beta-s 1, 2, or 3 results in an increase in the steady-state levels of the messenger RNAs for TGF-beta-s 2 and 3, but does not change expression of TGF-beta-4 mRNA. In contrast, in cultured cardiac myocytes, addition of TGF-beta-s 1, 2, or 3 results in an increase in expression of TGF-beta-s 3 and 4 mRNAs, but does not change expression of TGF-beta-2 mRNA. Moreover, expression of TGF-beta-s 2, 3, and 4 mRNAs is not affected by addition of any of the TGF-beta-s to fibroblasts. Addition of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), or interleukin-1 (IL-1) to these chicken cells also has differential effects on expression of the different TGF-beta mRNAs depending on the cell type. Retinoic acid also has contrasting effects on chondrocytes and myocytes either increasing or decreasing, respectively, expression of TGF-beta-s 2 and 3 mRNAs and TGF-beta-2 protein. Our results indicate a complex pattern of regulation of the different TGF-beta genes by themselves as well as by PDGF, EGF, IL-1, dexamethasone, TPA, and retinoic acid in chicken embryo cells.