Although grapefruit intake leads to elevated serum estrogen levels when hormones are taken orally, there are no published data on the effect on endogenous levels. We conducted a pilot dietary intervention study among healthy postmenopausal volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were recruited through the Love/Avon Army of Women. The study consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr after grapefruit intake were collected during an acute-phase study for 10 women. Serum assays for estrone (E1), estradiol (E2), estrone-3-sulfate (E1S), dehydroepiandrosterone sulfate, and sex hormone-binding globulin were conducted. Whole grapefruit intake had significant effects on endogenous E1S. Peak effects were seen at 8 hr, increasing by 26% from baseline. No changes in mean E1 or E2 with whole fruit intake were observed. In contrast, fresh juice, bottled juice, and soda intake all had significant lowering effects on E2. The findings suggest an important interaction between grapefruit intake and endogenous estrogen levels. Because endogenous estrogen levels are associated with breast cancer risk, further research is warranted.