Aldosterone regulates sodium reabsorption in epithelial tissues such as the kidney and colon, via a pathway involving the activation of intracellular mineralocorticoid receptors (MR), induction of specific target genes and a subsequent increase in sodium channel activity. Characterized aldosterone target genes in epithelia include the serum and glucocorticoid-regulated kinase 1 and the corticosteroid hormone-induced factor. Endothelin-1 (ET-1) is a potent vasoconstrictor that alters both sodium transport and hydrogen ion secretion in the kidney. Recent studies in a mouse medullary collecting duct cell line and rat A-10 smooth muscle cells have demonstrated an acute response of ET-1 gene expression to aldosterone. In the present study we have investigated the ET-1 gene in vivo as a potential direct aldosterone-regulated target gene in the kidney and colon. Adrenalectomized rats given a single dose of aldosterone were found to have a two fold increase in ET-1 mRNA levels in the kidney and colon after one hour. No significant changes in mRNA levels were detected for the related isoforms ET-2 or ET-3. Co-treatment with aldosterone and potassium canrenoate, a MR antagonist, blocked induction of ET-1 mRNA suggesting that induction was mediated via the MR. In a time course study, ET-1 mRNA levels were induced rapidly by aldosterone with levels of ET-1 mRNA maximally increased two fold and 2.5 fold after one hour in the kidney and colon respectively. These results suggest that ET-1 is a direct aldosterone gene target in the kidney and colon, and may play an important role in aldosterone-regulated ion homeostasis.