The importance of physiological ACTH stimulation in maintaining the response of aldosterone secretion to potassium was studied in 5 conscious sheep with cervical adrenal autotransplants. Endogenous ACTH secretion was suppressed by dexamethasone. Constant local infusions of potassium that raised adrenal venous plasma by 2 mmol/l increased aldosterone secretion from 3 +/- 1 ng/min (mean +/- SE) to levels of 50 +/- 13 ng/min at 30 min, after which secretion fell to 14 +/- 6 ng/min at 230 min. Addition of submaximal ACTH (0.04 - 0.10 mU/min) to potassium infusions produced similar responses at 0--130 min, but aldosterone secretion increased at 130--190 min and was more sustained (40 +/- 9 ng/min at 230 min; P less than 0.05). Infusions of submaximal ACTH alone did not significantly increase aldosterone secretion above basal levels. Infusions of maximal ACTH (16.6 mU/min) produced higher aldosterone secretion in the group given ACTH replacement. These results show that the aldosterone response to potassium is phasic and poorly sustained in the absence of ACTH. Responsiveness can be restored by doses of ACTH insufficient alone to stimulate aldosterone secretion.