Vaginal administration of 200 or 400 mg of progesterone in a wax suppository every 12 h in normal women was effective in rapidly achieving and maintaining serum progesterone concentrations at physiological levels appropriate to the midluteal phase of the ovarian cycle and early pregnancy. Given in the follicular phase for 5 days in five subjects at each of two doses, progesterone reached concentrations in serum after 4 and 12 h of 21-105 nmol/l (mean 46.4 nmol/l SD 17.2, n = 50) with 200 mg dosage and 21-101 nmol/l (mean 53.8 nmol/l SD 16.6, n = 49) with 400 mg dosage. There was no significant reduction in levels between 4 and 12 h after administration, in contrast to previously reported findings, suggesting that the wax base led to slow release of the hormone. The uptake of progesterone in the midluteal phase was assessed in 10 subjects by comparing successive cycles treated with progesterone or placebo in a randomized double-blind manner. Using only the 400 mg dosage, the mean serum progesterone level was raised by 69%, the untreated level being normal (38.17 SD 10.01 compared with 64.49 SD 23.22 nmol/l, n = 10). This was despite an assumed concomitant fall in endogenous hormone production as suggested by a 28% reduction in oestradiol-17 beta levels. Thus vaginal administration of progesterone in wax appears to be effective and convenient, and preferable to the use of other progestogens in various circumstances in which a fetus may be exposed to the drug.