Tropomyosins are a closely related family of proteins with a dimeric α-coiled-coil structure1. Skeletal isoforms are composed of two types of subunits, α and β2-4 which, in turn, are assorted into two main molecular species αα and αβ5-7. Both isoforms are present in different molar ratios in individual skeletal muscle types8,9. In small mammals, however, onlyα-chain is expressed in cardiac muscle8. Tropomyosin, in association with the troponin complex (troponin-I, -T and -C) plays a central role in the Ca2+dependent regulation of vertebrate striated muscle contraction10-12. On the other hand, despite structural similarities with the striated isoforms, the function of this protein in smooth muscle and non-muscle cells remains unknown, because in these cells contraction is thought to be regulated by myosin-linked processes independently of tropomyosin13-15. Here we report the nucleotide sequences of cloned complementary DNAs for rat striated and smooth muscle α-tropomyosin. Comparison of the derived amino-acid sequences reveals the existence of tissue-specific peptides that delimit the putative troponin-I and troponin-T binding domains of tropomyosin. S1-nuclease mapping studies reveal the existence of three distinct α-tropomyosin messenger RNA isoforms each encoding a different protein; these isoforms are tissue-specific, developmentally regulated and most probably encoded by the same gene.