Dietary supplements containing black cohosh are alternatives to conventional hormone replacement therapy. This study investigates the maximum tolerated dose of a 75% ethanol extract of black cohosh and determines the pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26-deoxyactein. Single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg of 23-epi-26-deoxyactein were administered to three groups of five women each. Serial blood draws and 24 h urine samples were obtained; blood chemistries, hormonal levels, and 23-epi-26-deoxyactein levels were determined. No acute toxicity or estrogenic hormone effects were observed. Pharmacokinetic analysis of 23-epi-26-deoxyactein in serum indicated that the maximum concentration and area under the curve increased proportionately with dosage, and the half-life was approximately 2 h for all dosages. Less than 0.01% of the 23-epi-26-deoxyactein was recovered in urine 24 h after administration. No phase I or phase II metabolites were observed in clinical specimens or in vitro.