To examine the question of the tubular localization of renal endothelin-1 (ET-1) mRNA, cDNA generated by reverse transcription of isolated rat tubule RNA was amplified by polymerase chain reaction using rat ET-1-specific oligonucleotides. Product identity was determined by restriction enzyme digestion or direct product sequencing. ET-1 mRNA was found to increase in renal tissue in a corticomedullary direction. High levels of ET-1 mRNA were found in dissected glomeruli and in juxtaglomerular cells in short-term primary culture. Among tubule segments, ET-1 mRNA was most abundant in inner medullary collecting ducts (IMCD), but products were also found with cDNA derived from proximal convoluted and straight tubules, thick ascending limbs, and outer medullary collecting ducts. In kidneys of untreated, homozygous Brattleboro rats, the increase of ET-1 mRNA along the corticomedullary axis as well as the preponderance of tubular ET-1 mRNA in IMCD was not observed. Our data show that ET-1 mRNA is present in all nephron segments studied and that its expression may be dependent on the functional state of the kidney. Our results are consistent with the proposal that ET-1 modifies tubular function in an autocrine or paracrine fashion.