TGF‐β1, like basic and acidic fibroblast growth factor (FGF), inhibits differentiated gene expression in skeletal myoblasts. It potentiates FGF induction of skeletal muscle in embryonal mesoderm. In cardiac muscle, TGF‐β1 down‐regulated expression of the α‐myosin heavy chain gene and the sarcoplasmic reticulum calcium ATPase gene, yet up‐regulated expression of the genes for β‐myosin heavy chain, atrial natriuretic factor, and both skeletal and smooth muscli: α‐actin—four transcripts associated with the embryonic heart. TGF‐β1 did not affect cardiac α‐actin gene expression. These responses resemble the generalized ‘fetal’ phenotype seen during hypertrophy triggered by a haemodynamic load. Chick skeletal and cardiac α‐actin promoter‐driven reporter genes were transfected into neonatal rat cardiac myocytes. TGF‐β1 stimulated skeletal α‐actin transcription, but not transcription from the cardiac α‐actin promoter. Basic FGF produced the same results as TGF‐β1, but acidic FGF suppressed expression of both α‐actin genes; these results were true for purified and recombinant FGFs. Modulation of α‐actin transcription by growth factors corresponded accurately to control of the endogenous genes. Three positive cis‐acting elements were critical for skeletal α‐actin transcription in cardiac, as well as skeletal, myocytes, particularly the downstream CCAAT box‐associated repeat. Thus, TGF‐β1 and FGFs selectively induce an ensemble of ‘fetal’ genes anti differentially regulate α‐actin transcription in cardiac muscle cells.