OBJECTIVE To study the pharmacokinetics of progesterone (P) in healthy premenopausal female volunteers to compare the bioavailability of orally or vaginally administered hormone. METHODS Subjects were randomly allocated to receive either oral P or a vaginal pessary then crossed over to the alternate preparation 1 month later. METHODS The study was conducted in outpatient setting. METHODS All subjects were healthy, normal female volunteers who underwent a physical and gynecological examination before the study. None were using oral contraceptives. Ten subjects (mean age 32.6 +/- 7.3 years) entered the study and all completed it. METHODS Progesterone was administered as 200 mg of micronized hormone or as a pessary containing 400 mg. METHODS Plasma levels of P were measured by radioimmunoassay to test the apriori hypothesis of similar bioavailability. RESULTS Peak plasma P concentrations attained within 4 hours after oral administration ranged from 8.5 to 70.6 ng/mL, whereas after vaginal administration the peak levels were attained within 8 hours and ranged from 4.4 to 181.1 ng/mL. Considerable interindividual variation was noted. Area under the plasma concentration-time curve for the two formulations was not significantly different (F = 1.09; P greater than 0.1; ANOVA). CONCLUSIONS The two formulations had similar bioavailability.