Moxestrol, the 11 beta-methoxy derivative of ethynyl estradiol and a highly potent estrogen, is rapidly distributed in the body (AIVD = 148.6 +/- 19.71, MCR = 79.9 +/- 10.5 1/h) after i.v. administration because it is not bound by SBP and has low affinity for albumin. Its oral bioavailability is about 33% after administration of 30 or 100 micrograms to healthy volunteers and slightly lower than that of ethynyl estradiol (50%) due to a "first-pass effect". Moxestrol is rapidly metabolized by the liver as shown by the much increased bioavailability (60.5%) in patients with impaired liver function. The radioimmunoassay for moxestrol measures plasma moxestrol levels ranging from 100 pg/ml (maximum) to 10 pg/ml (24 h value) after treatment with a 100 micrograms commercial formulation (Surestryl). Moxestrol metabolism was studied on urine which contained 28% of administered radioactivity after i.v. or oral administration. Hydroxylation was the main transformation pathway as for ethynyl estradiol. Moxestrol yielded metabolites hydroxylated (or methoxylated) at C-2, C-15 and C-16, but not at C-6, and also gave rise to D-homo derivatives. The main difference between moxestrol and ethynyl estradiol lies in the relative importance of these pathways. The presence of the ethynyl group of ethynyl estradiol impedes attack at C-16 and hydroxylation at C-2 to form catechol estrogens becomes a major pathway, whereas the 11 beta-methoxy group of moxestrol impedes hydroxylation at C-2 and ring D hydroxylated products of moxestrol are formed. The low amount of catechol estrogens obtained with moxestrol compared to ethynyl estradiol could have important physiological implications in the human.