RU 486 (17 beta-hydroxy-11 beta-[4-dimethylamino phenyl]-17 alpha-[1-propynyl]estra-4,9-dien-3-one) is a clinically useful glucocorticoid and progesterone antagonist. The authors studied the pharmacokinetic properties of this drug in normal volunteers and patients with Cushing's syndrome using a rat progesterone radioreceptor assay. This assay gave values similar to those obtained with a rat glucocorticoid radioreceptor assay. After a single oral dose of 25 mg/kg (n = 11) or 10 mg/kg (n = 11) to normal volunteers, plasma concentrations of progesterone receptor-reactive material reached maximal levels of 754 +/- 288 (mean +/- S.D.) and 517 +/- 183 micrograms/dl. This occurred at 3.1 +/- 1.9 and 2.5 +/- 1.0 h, respectively. The respective apparent plasma half-lives were 19.2 +/- 7.0 and 20.6 +/- 7.7 h. Four patients with Cushing's syndrome treated chronically (10-20 mg/kg/day) had relatively constant plasma levels of receptor reactivity ranging from 506 to 1184 micrograms/dl. Chromatographic characterization of circulating receptor reactivity showed that the active fraction corresponded to RU 486 and its hydrophilic N-mono- and N-didemethylated metabolites. Less than 0.5% of the daily dose was excreted in the urine of two of these patients as receptor reactivity. The drug bound extensively to circulating albumin, which competed with the glucocorticoid receptor of intact human mononuclear leukocytes for [3H]RU 486 in a concentration-dependent manner.