Concentrations of total and weakly bound plasma estradiol were significantly (P less than .01) reduced in 73 healthy post-menopausal women after 10-22 weeks of participation in a low-fat diet intervention program. Nonsignificant reductions in estrone sulfate and sex hormone-binding protein were also observed. The 17% reduction in average estradiol concentration was accompanied by an average reduction of 12 mg/dL in total plasma cholesterol (P less than .001), an average weight loss of 3.4 kg (P less than .001), and an average reduction in daily dietary fat from 68.5 to 29.5 g. Our review of case-control studies indicates that a 17% reduction in plasma estradiol may explain a noteworthy component of the international variation in breast cancer incidence. We find a need for further studies of (a) disease risk in relation to hormone concentrations and (b) changes in hormone concentrations as a function of the duration of low-fat diet intervention.