In potassium-depleted rats lithium is reabsorbed by an amiloride-sensitive transport mechanism in the distal nephron segments, and the urinary fractional excretion of lithium (FE[Li]) is reduced by almost 50% compared to that of potassium-replete rats. We have used renal clearance techniques to study the effects of adrenalectomy (Adx) or sham operation on amiloride-sensitive lithium reabsorption in conscious potassium-deprived (K5) and control (K200) rats. In the sham-operated rats, administration of a low potassium diet led to a significant reduction in FE(Li) from 27.0 to 16.6% (p < 0.01), whereas in the Adx rats the reduction in FE(Li) was smaller (from 27.0 to 22.6) and not statistically significant. Urinary sodium excretion was similar (1,100 nmol/min/100 g body weight) in all groups. During subsequent amiloride infusion in order to block the distal nephron reabsorption of lithium, urinary sodium excretion increased nearly twofold in the sham-operated groups whereas no change was evident in the Adx rats. Similarly, amiloride led to an increase in FE(Li) in the sham-K5 group but failed to increase FE(Li) in the Adx-K5 group. The results suggest that amiloride-sensitive lithium transport seen during potassium depletion is influenced by the presence of the adrenal glands, most likely due to their production of aldosterone.