In a series of randomized crossover studies, we examined the pharmacokinetics of daidzein and genistein in healthy adults fed different amounts and types of soy foods. These studies were designed to address whether all soy isoflavone are equal in terms of their apparent bioavailability. Classical pharmacokinetics have established that the volume of distribution in adults is large, indicating a wide tissue distribution, and that the shape of plasma appearance curve is consistent with compounds that undergo enterohepatic recycling. Peak concentrations are seen generally 4–8 h after dietary intake, and the plasma appearance and disappearance in pre- and postmenopausal women are similar. Most of the daidzein and genistein is excreted within the first 24 h, with the average fractional excretion remaining relatively constant over a wide range of intakes, although there is a high individual variability, ranging from 20 to 50% of the dietary intake. Differences are observed in the elimination half-life for different foods. More rapid elimination is observed for isoflavones in a liquid matrix than in a solid matrix food. The bioavailability as determined from the area under the curve is therefore influenced by the food matrix. We have found a curvilinear relationship between the dietary intake of isoflavones and peak plasma concentration and apparent bioavailability, indicating that absorption of isoflavones from food may be saturable. It may be more difficult to attain supraphysiologic levels of isoflavones from foods than from supplements, which are more closely aligned with pharmacologic agents. These findings are relevant to the safety of phytoestrogens. On the basis of the pharmacokinetics of soy isoflavones, maintenance of high steady-state plasma concentrations will be achieved by a regular intake, particularly if phytoestrogens are ingested throughout the day. This approach may serve to maximize the efficacy of phytoestrogens in clinical studies.