We have investigated the expression of transforming growth factor (TGF)-beta 1,-beta 2, and -beta 3 in developing, degenerating, and regenerating rat peripheral nerve by immunohistochemistry and Northern blot analysis. In normal adult sciatic nerve, TGF-beta 1, -beta 2, and -beta 3 are detected in the cytoplasm of Schwann cells, and the levels of TGF-beta 1 and -beta 3 mRNAs are constant during post-natal development. When sciatic nerves are transected to cause axonal degeneration and prevent axonal regeneration, the level of TGF-beta 1 mRNA in the distal nerve-stump increases markedly and remains elevated, whereas the level of TGF-beta 3 mRNA falls modestly and remains depressed. When sciatic nerves are crushed to cause axonal degeneration and allow axonal regeneration, the level of TGF-beta 1 mRNA initially increases as axons degenerate, and then falls as axons regenerate. TGF-beta 2 mRNA was not detected in developing or lesioned sciatic nerves at any time. Cultured Schwann cells have high levels of TGF-beta 1 mRNA, the amount of which is reduced by forskolin, which mimics the effect of axonal contact. These data demonstrate that Schwann cells express TGF-beta 1, -beta 2, and -beta 3, and that TGF-beta 1 and -beta 3 mRNA predominate over TGF-beta 2 mRNA in peripheral nerve. Axonal contact and forskolin decrease the expression of TGF-beta 1 in Schwann cells.