Transforming growth factors (TGF) are potent multifunctional polypeptides that are involved in renal function and glomerular sclerosis. We postulated that dietary salt modified renal production of TGF-β. An increase in dietary salt produced sustained increases in steady-state levels of mRNA for TGF-β1, -β2, and -β3 in the rat kidney. While serum concentration of TGF-β1 did not change, the 8.0% NaCl diet increased urinary excretion of TGF-β1, indicating enhanced renal production was the source of TGF-β1. Increasing urinary flow rates with diuretics did not further increase synthesis of TGF-β1 in animals receiving the 8.0% NaCl diet. The 8.0% NaCl diet increased production of TGF-β1 in both glomeruli and tubules, although active TGF-β1 was secreted in greater amounts only from glomeruli. Enhanced glomerular production of both inactive and active TGF-β1 induced by the 8.0% NaCl diet was inhibited by tetraethylammonium (TEA) and not glybenclamide. Cardiac production of TGF-β1 also increased on the 8.0% NaCl diet but was not affected by TEA. The results demonstrated that increased dietary salt augmented glomerular TGF-β production by a mechanism that included a TEA-sensitive potassium channel. Dietary salt, by facilitating glomerular expression of TGF-β, may directly promote development of glomerulosclerosis.