The role of augmented aldosterone production in pregnancy is poorly understood. Whereas some consider aldosterone secretion in pregnancy excessive, others suggest that this is a compensatory phenomenon. According to yet another view, mechanisms other than the renin-angiotensin-aldosterone system control sodium homeostasis in pregnancy. Metabolic balance studies were performed on 14 3rd trimester women. Mineralocorticoid activity was experimentally increased by administering desoxycorticosterone acetate, 9alpha-fluorocortisol acetate, or ACTH for 4-12 days. Administration of mineralocorticoid or ACTH consistently caused sodium retention. During this mineralocorticoid-induced volume expansion, aldosterone excretion decreased markedly. Natriuresis, which followed discontinuance of the drug, continued while aldosterone excretion, although greatly diminished compared to control values, was greater than that found in normal, nonpregnant individuals. This saline diuresis did not subside until aldosterone excretion returned to its previously high control values. These observations support the concept of the physiological role of increased aldosterone production in pregnancy. Results further revealed a marked dissociation between antinatriuretic and kaliuretic effects of corticoids. Potassium balance was virtually unaltered during continued mineralocorticoid or ACTH administration, despite initially high or abruptly increased sodium intakes. Finally, mineralocorticoid escape was induced by continued desoxycorticosterone acetate therapy in two male volunteers. Kaliuresis occurred which was subsequently abolished when progresterone was administered. Sodium excretion, however, was virtually unaltered. These data, mimicking results observed in gravidas, suggest that progesterone is an important determinant of potassium homeostasis in pregnant women.