Background. Tamm-Horsfall glycoprotein (THP) is a unique protein that is produced exclusively by cells of the thick ascending limb of Henle's loop (TALH). This study examined whether dietary salt altered renal THP production. Methods. Male Sprague-Dawley rats were examined on days 1, 4, and 15 following placement in metabolic cages on diet that contained 0.3%, 1.0% or 8.0% NaCl. THP expression was quantified using Northern hybridization and Western blotting analysis. Results. An increase in dietary salt produced sustained increases in relative steady-state mRNA and protein levels of THP in the kidney. Addition of furosemide, but not chlorothiazide, to animals on the 8.0% NaCl diet further augmented steady-state mRNA levels of THP. Conclusions. An increase in dietary salt and the loop diuretic, furosemide, increased expression of THP in the rat. The data support the involvement of this unique protein in the function of the TALH during changes in dietary salt. These findings also suggest that restriction of dietary salt may be beneficial in cast nephropathy in multiple myeloma and recurrent nephrolithiasis, two diseases in which THP can play an important pathogenetic role.