Soybean consumption may be protective for breast cancer, possibly due in part to the presence of the isoflavones daidzein and genistein, which are weakly estrogenic. The metabolism and disposition of these phytoestrogens during chronic soya exposure were studied on a metabolic unit. Six healthy 22- to 29-year-old women consumed an unrestricted hospital diet for most of the study and ingested 12 oz of soymilk with each meal for one month. At two-week intervals, excretion of isoflavones in urine was studied, during which time the subjects consumed a constant basal diet for three to four days, ingested the full daily 36-oz portion of soymilk within 30 minutes each day for one to two days, and collected urine continuously. Urinary recovery of genistein [initially 23.9 +/- 17.3% (SD) of ingested genistin + genistein], daidzein (initially 66.2 +/- 23.5% of ingested daidzin + daidzein), and equol (initially 28% of the ingested precursors daidzin + daidzein in 1 subject and < 1% in 5 subjects) decreased progressively over four weeks of daily soya ingestion by 42% for genistein (p < 0.05) and 31% for daidzein (p < 0.01) but increased by 3- to 100-fold for equol (4 subjects, p < 0.05). Total amounts excreted and peak levels were similarly affected. The absorption half-lives (t 1/2) for genistein and daidzein were initially 2.7 +/- 0.8 and 1.6 +/- 0.5 hours, respectively, and during four weeks of soymilk ingestion decreased to 2.0 +/- 0.6 (p = 0.04) and 1.4 +/- 0.2 hours (p = 0.06), respectively, suggesting more rapid absorption. The appearance t 1/2 of equol can be estimated for only one subject initially (2.9 hrs), but during four weeks of soya ingestion it could be estimated for three more subjects (4.7 +/- 2.3 hrs). The excretion t 1/2 values for genistein and daidzein were initially 6.7 +/- 0.8 and 4.4 +/- 0.7 hours, respectively, and during four weeks of soymilk ingestion decreased to 4.2 +/- 1.2 (p = 0.005) and 3.2 +/- 1.1 hours (p = 0.005), respectively, suggesting more rapid excretion. For equol, the excretion t 1/2 was initially 9.1 hours (1 subject), and after two and four weeks of soymilk ingestion it was 13.4 +/- 9.7 and 5.5 +/- 1.6 hours (4 subjects, p = 0.046, 2 wks vs. 4 wks), respectively. These results indicate that metabolism and disposition of ingested isoflavones are altered during chronic soya ingestion in women, perhaps from increased metabolic degradation to formation of nonisoflavone metabolites. Increased production of the longer- and stronger-acting estrogenic equol in some women during chronic soymilk ingestion may alter the estrogenic potency of dietary soya isoflavones.