Using a muscle cell line and satellite cell cultures, it has been shown that transforming growth factor-β (TGF-β) has a powerful inhibitory effect on myoblast replication and differentiation. However, little work has been done on the possible role of TGF-β in adult muscle in vivo. Using Western blot and immunohistochemical analyses, we investigated normal distribution of TGF-β2 and TGF-βRII proteins between slow and fast-type muscles, and the adaptive response of these proteins in the mechanically overloaded muscles, in the regenerating muscles following bupivacaine injection and in the denervated muscle after section of sciatic nerve. Slight TGF-β2 immunoreactivity was detected both in slow- and fast-type muscles of mature rat. The amount of TGF-βRII protein was markedly greater in fast-type muscles. In the overloaded muscle, immunohistochemical analysis showed a marked increase in TGF-β2 immunoreactivity in the mononuclear cells (probably endothelial and perithelial or smooth muscle cells of endomysial capillaries) of the extracellular space at 3 and 6 days post surgery. Rapid increase of TGF-β2 protein and concomitant decrease of the receptor (TGF-βRII) were observed in the mechanically overloaded and regenerating muscles. On the other hand, denervation of slow- and fast-type muscles showed a rapid increase in TGF-β2 protein, but did not elicit a concomitant decrease of TGF-βRII. These results indicate that TGF-βRII is preferentially distributed in fast-type muscles. Furthermore, TGF-β2 may play an important role in muscle hypertrophy and regeneration by the usage of TGF-βRII.