Studies have been carried out in human volunteer subjects to evaluate the role of aldosterone in the development, maintenance, and correction of metabolic alkalosis induced by selective depletion of hydrochloric acid. During the first phase of our study the rate of aldosterone secretion was measured before the induction of alkalosis (while the subjects were on a low salt diet) and again after a steady state of metabolic alkalosis had been established. The data demonstrate a fall in aldosterone secretion from a value of approximately 500 mug/day to a value of approximately 200 mug/day. Thus, it appears that an increased rate of aldosterone secretion is not a prerequisite to the elevation of the renal bicarbonate threshold. During the second phase of our study, aldosterone was administered to the alkalotic subjects in doses of 1000 mug/day (or deoxycorticosterone acetate in doses of 40 mg/day) in order to determine the effects of a persistent steroid excess on the ability of sodium chloride to correct the acid-base disturbance. The data demonstrate that despite the administration of steroid, the ingestion of sodium chloride led to a reduction in plasma bicarbonate concentration from 39 to 29 mEq/liter, accompanied by a suppression of renal acid excretion. This reduction in plasma bicarbonate concentration occurred without a concomitant retention of potassium, a deficit of as much as 400-500 mEq of potassium persisting during repair of the acid-base disturbance. Our findings suggest that "saline-resistant" alkalosis, when it occurs in the absence of primary hyperadrenalism, cannot be attributed to aldosterone excess and/or potassium depletion of the magnitude seen in our study. We also suggest the need for a reappraisal of the way in which aldosterone excess contributes to the genesis and maintenance of alkalosis in primary aldosteronism.