1. Renal tubules and, in particular, the inner medullary collecting duct, produce endothelin and express cognate receptors. 2. Endothelins inhibit vasopressin-stimulated cAMP accumulation and water reabsorption in the collecting duct; endothelins may also inhibit sodium reabsorption in the proximal tubule and collecting duct. 3. Autocrine inhibition of sodium and water reabsorption in the inner medullary collecting duct by endothelin may play a role in maintaining extracellular fluid volume homeostasis. 4. Derangements in autocrine inhibition of sodium and water reabsorption in the inner medullary collecting duct by endothelin may be involved in the pathogenesis of the hypertensive state. 5. Nephron-derived endothelins may function in a paracrine manner to regulate interstitial, juxtaglomerular and vascular smooth muscle cell function.