Considerable evidence indicates that the cortical collecting tubule is a target epithelium for aldosterone. Isolated perfused cortical collecting tubules from rabbits given large doses of deoxycorticosterone acetate (DOCA) for several days, or whose endogenous production of aldosterone is increased by dietary means, exhibit large lumen-negative transepithelial voltages, increased sodium (Na) absorption, and increased potassium (K) secretion compared with tubules from normal animals. However, controversy exists regarding the response of this nephron segment to acute in vitro administration of aldosterone. To address this issue we performed three groups of experiments: 1) clearance experiments on adrenalectomized rabbits to determine the minimum time required after in vivo aldosterone administration before significant changes in sodium excretion are observed; 2) microperfusion experiments on cortical collecting tubules from normal and adrenalectomized rabbits in which transepithelial voltage was measured before and after adding aldosterone to the bath; 3) microperfusion experiments on cortical collecting tubules from adrenalectomized rabbits in which transepithelial voltage, sodium and potassium flux were measured before and after in vitro exposure to aldosterone or dexamethasone. The clearance studies demonstrate that after a 2 hr latent period aldosterone produces significant antinatriuresis without change in K excretion. In vitro studies failed to reveal a steroid-induced change in the transepithelial voltage of cortical collecting tubules from either normal or adrenalectomized rabbits. However, aldosterone added in vitro to collecting tubules from adrenalectomized rabbits produced an increase in net Na absorption without a significant change in voltage or K secretion.(ABSTRACT TRUNCATED AT 250 WORDS)