Purpose: While tamoxifen has been shown to alter concentration of many hormones and their binding globulins, there have been conflicting results regarding its effects on thyroid function tests. We sought to clarify these effects by studying subjects in a controlled clinical trial. Patients and Methods: We evaluated a subset of postmenopausal women who had participated in a longitudinal, double-blind, randomized, placebo-controlled toxicity study of tamoxifen 10 mg orally, twice daily. There were 14 subjects in both the tamoxifen and placebo groups. Measurement of thyroid-binding globulin (TBG), thyroxine uptake (T-Uptake), thyroxine (T-4), and thyroid-stimulating hormone (TSH), and an indirect estimate of the free T-4 index (FTI), were made for each subject before and after 3 months of treatment. Results: For T-Uptake, T-4, and TBG, there were significant increases in the mean change from baseline to 3 months in the tamoxifen group compared with the placebo group (P = .02, .0001, and .003, respectively), while there were no significant changes in the measured TSH and in the calculated FTI. Conclusion: We conclude that tamoxifen therapy in postmenopausal women results in increased TBG, with secondary increases in measured T-Uptake and T-4 following. However, TSH and FTI levels are unchanged, and treated women remain eumetabolic. J Clin Oncol 13:854-857. (C) 1995 by American Society of Clinical Oncology.