OBJECTIVE: To investigate the pharmacokinetic profiles of different doses of micronized 17 beta-estradiol administered by oral or sublingual routes. METHODS: Single doses of micronized 17 beta-estradiol were administered orally (1 mg, 0.5 mg) or sublingually (1 mg, 0.5 mg, 0.25 mg) to six postmenopausal women in a randomized clinical trial. We calculated pharmacokinetic parameters for estradiol (E2) and estrone (E1) of maximum serum concentration, time to maximum serum concentration, terminal half-life, area under the concentration curve, and oral clearance. Serum levels of E1 sulfate also were compared at 4, 12, and 24 hours after dosing. RESULTS: Sublingual administration resulted in rapid absorption with significantly higher E2 levels than did comparable oral dosing. Estrone levels did not vary with route of administration but correlated with the dosage administered. Estrone sulfate levels correlated with the dosage administered and also tended to be higher with sublingual administration. Sublingual administration resulted in a significantly lower E1 to E2 ratio during the 24 hours than did oral administration. CONCLUSION: Sublingual administration of micronized 17 beta-estradiol results in a rapid, burst-like absorption into the systemic circulation, yielding high E2 levels that fall rapidly over the first 6 hours.