Despite the safety review conducted by the U.S. Food and Drug Administration in the process of awarding a health claim for the cholesterol-lowering properties of soy protein, concerns about the possible goitrogenic effects of soybean isoflavones persist. Concerns are based primarily on in vitro research, animal studies, and older reports of goiter in infants fed soy formula not fortified with iodine. In a randomized, double blind, placebo-controlled study, we investigated the effect on thyroid function of a daily supplement containing 90 mg (aglycone weight) of total isoflavones/day versus placebo in 38 postmenopausal women, 64-83 years old, not on hormone replacement therapy. Serum thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) were measured at baseline and after 90 and 180 days. In the supplement group, at baseline and 6 months, TSH (micro U/ml), T4 (nM), and T3 (nM) levels (mean +/- SE) were 3.00 +/- 0.44, 149.00 +/- 5.04, and 1.53 +/- 0.13, respectively, and 3.49 +/- 0.52, 154.52 +/- 2.09, and 1.78 +/- 0.12, respectively. In the control group, levels at baseline and at 6 months were 3.35 +/- 0.51, 145.39 +/- 6.69, and 1.55 +/- 0.18, respectively, and 3.63 +/- 0.57, 153.77 +/- 6.64, and 1.75 +/- 0.10, respectively. Intragroup differences for all three measures were statistically indistinguishable at 6 months, and levels were similar between the isoflavone supplement and placebo groups at each measurement. These results indicate that in this group of healthy iodine-replete subjects, soy isoflavones do not adversely affect thyroid function.