The primary mechanism of steroid hormone action in vertebrates involves hormone binding to its receptor followed by receptor phosphorylation and dimerization. This activated receptor then produces enhancer actions through hormone response elements (HREs) in the promoter region of hormone-regulated genes and results in subsequent gene transactivation or inactivation. It is important to know which chemicals in the environment mimic or inhibit hormone activity, what structural properties of these chemicals play a role in this activity, and what effects these compounds may have on the hormone-responsive processes in human development and disease. While environmental chemicals have been implicated in the etiology of many hormone-regulated human diseases, the many possible nuclear receptor mediated mechanisms involved remain to be characterized It is known that certain xenobiotics can alter normal estrogen activity through interactions with the estrogen receptor (hER). This process involves receptor binding with specific estrogen response elements (EREs) in the promoter of genes. All EREs are derivatives of the 13-mer palindromic consensus ERE originally identified from the Xenopus and chicken vitellogenin genes. It has been proposed that xenobiotics may activate estrogen-regulated genes selectively, depending on the sequence of the ERE in the promoter. While the estrogen activity of many environmental chemicals has been evaluated in a wide range of in vivo and in vitro assays, the capacity for xenobiotics to differentially activate genes regulated by non-consensus EREs has been poorly characterized. Since progesterone receptor (hPR) is an ER-dependent gene, it is also very important to determine if xenobiotics with estrogen activity can alter transcriptional transactivation of genes via hPR interactions and the progesterone response element (PRE). While there have been some reports of environmental chemicals, such as metabolites and isomers of the pesticide dichlorodiphenyltrichloroethane (DDT), interacting with the hPR, none of these studies evaluate the effects of other types of environmentally relevant xenobiotics with more diverse structure on hPR-regulated gene activation. In addition, the concept of tissue-selective gene activation by endocrine disrupting chemicals has not been well examined. This dissertation tests the hypothesis that xenobiotic chemicals may selectively regulate hormone-responsive genes depending on promoter content (hormone response element sequence) and that this activity may be mediated differently by multiple steroid receptors (hER and hPR) in a tissue or cell specific manner