The present study is concerned with the regulation of free plasma oestradiol in relation to maternal adrenal function during late human pregnancy. Blood was collected in 9 patients at short time intervals of 30 min from 17 h to 3 h. In order to exclude endogenous ACTH-secretion 5 patients received 12 mg dexamethasone over 48 h. Between 20 h and 2 h 0.25 mg ACTH1-24 (Synacthen) was infused into the subjects. Non-conjugated oestradiol was determined by radioimmunoassay and total plasma cortisol by protein binding method. During the application of ACTH free oestradiol increased from 21.3 +/- 5.7 to 25.5 +/- 7.1 ng/ml (P less than 0.025) in the patients without dexamethasone. The increase was moderately correlated to rising cortisol (r = 0.58, P less than 0.001). Plasma oestradiol reached its maximum level after 90 min, followed by a tendency to decline despite persisting stimulation of maternal adrenals. The patients receiving dexamethasone exhibited during ACTH-infusion a rise of oestradiol from 3.8 +/- 1.9 to 7.8 +/- 3.1 ng/ml (P less than 0.001). Increasing oestradiol was strongly correlated to plasma cortisol (r = 0.67, P less than 0.001). The phenomenon of earlier declining oestradiol levels did not occur. These results suggest that maternal adrenals predominantly regulate the formation of free oestradiol. Plasma cortisol indicating maternal precursor production balances the increase of oestradiol by suppressing foetal precursor supply.