Genistein, an isoflavone and phytoestrogen predominantly found in soy, is considered a potentially safe therapeutic option to prevent postmenopausal bone loss. A novel purified product consisting of 99.4% synthetic genistein aglycone was investigated in a phase 1 clinical study to assess safety and tolerability in healthy volunteers as well as to obtain pharmacokinetic data. Single oral doses of 30, 60, 150, or 300 mg were administered to 40 healthy volunteers in this prospective, randomized, open-label and sequential-group study. Tolerability of the different genistein doses was very good. No clinically significant effects on vital signs, ECG, and clinical laboratory parameters were observed. Genistein was rapidly absorbed and the kinetic profiles revealed a one-peak plasma concentration-time course. Mean Cmax values of 252.0, 605.0, 1518.0, and 1808.0 ng/mL were observed after 4.0 to 6.0 hours. The mean terminal elimination half-lives were calculated to be 7.7, 7.5, 8.1, and 10.2 hours resulting in mean AUCs(0-infinity) of 2761.8, 8022.3, 21655.0, and 27537.8 ngxhr/mL. Linear regression of the dose-normalized AUCs(0-infinity) was not significantly different from zero, whereas the analysis for Cmax showed significance. Based on consecutive administration of single oral doses of genistein, dose linearity was assumed for extent of absorption [AUC(0-infinity)] for all doses (30-300 mg) and for rate of absorption (Cmax) up to 150 mg. At the highest dose the intestinal rate of absorption of genistein seemed to be limited. Genistein was safe and well tolerated in the dose range investigated and showed nearly dose-linear pharmacokinetic characteristics.