Renin release is increased in the adrenalectomized rat and is not inhibited by sodium chloride administration. The purpose of this study was to determine whether increased renin release is related to impaired absorptive chloride transport in the loop of Henle. Chloride transport in the loop was measured before and after acute saline infusion in three groups of rats: 1) saline-drinking adrenalectomized rats (Adx); 2) saline-drinking dexamethasone-treated adrenalectomized rats (Dex); and 3) water-drinking sham-operated controls. Unrelated to differences of arterial pressure, glomerular filtration rate, or net sodium chloride balance, chloride reabsorption in the loop of Henle of Adx [836 +/- 172 peq/min (SE)] was less (P less than 0.01) than in controls (1,646 +/- 353) and Dex (1,377 +/- 318) before saline infusion. After saline infusion, chloride delivery to the loop increased (P less than 0.05) in all three groups. However, loop chloride reabsorption increased (P less than 0.01) only in controls and Dex but not in Adx. Before saline infusion, plasma renin concentration (PRC) of Adx (350 +/- 108 U/ml) was greater (P less than 0.01) than that in controls (56 +/- 6) or Dex (108 +/- 36); sodium chloride infusion failed to inhibit PRC in Adx, whereas PRC was suppressed (P less than 0.01) by saline in Dex and controls. Thus stimulation of renin release in adrenalectomized animals was associated with decreased absorptive chloride transport in the loop of Henle. Dexamethasone normalized loop function and renin responsiveness to sodium chloride.