Prostate cancer is the most frequently diagnosed cancer in American men and the second leading cause of cancer deaths. Supplementation with Se has reduced the incidence of prostate cancer and Se status is inversely correlated with prostate cancer risk. One molecular mechanism by which high Se concentrations may affect cancer risk is by catalyzing disulfide bond formation or otherwise complexing with reactive sulfhydryl groups in cellular proteins. The estrogen receptor (ER) contains cysteines in zinc (Zn) fingers that are susceptible to oxidation and internal disulfide formation, which can prevent DNA binding. We examined ER binding to its DNA response element and gene expression levels for estrogen-regulated genes in human prostate cancer cells (LNCaP) treated with control (50 nM) or high (5 ìM) concentrations of Se. High Se treatment resulted in a non-significant 16 % decrease in ER binding to the estrogen response element (ERE), and no significant changes were found in expression levels of estrogen-regulated genes for either run-on nuclear transcripts or total mRNA. The well documented reaction of Se with reactive sulfhydryl groups, if it occurs in the ER in vivo, has a minimal effect on the binding of ER to DNA and its regulation of gene expression.