Scientific edence suggests that humans and wildlife speces may experience adverse health consequences from exposure to environmental chemicals that interact with the endocrine system. Reliable short-term assays are needed to identifr hormone-dismpting chemicals. In this study we demonstrate that the estrogenic activity of a chemical can be evaluated by assaying induction or repression of endogenous estrogen-regulated 'marker genes" in human breast cancer MCF-7 cells. We induded four marker genes in the assay -pS2, transforming growth factor P3 (TGa933), monoamine oxidase A, and ecl-antichymotrypsin-and we evaluated estrogeniic acivity for 17P-estradiol (E2), diethylstilbestrol, ci-zearalanol, nonylphenol, genistein, methoxychlor, endosulphan, o,p-DDE, bisphenol A, dibutylphthalate, 4-hydoxy tamoxifn, and ICI 182.780. All four marker genes responded strongly to the three high-potency estrogens (E29diethylstilbestol, and -earalanol), whereas the potency of the other chemicals was 103-to 106-fold lower than that of E2. There were some maker gene-dependent differences in the relative potencies of the tested chemicals. TG$P3 was equally sensitive to the three high-potency estrogens, whereas the sensitivity to oc-zearalanol was approximately 10-fold lower than the sensitivity to E2 and diethyistilbestrol when assayed with the other three marker genes. TIhe potency of nonylphenol was equal to that of genistein when assayed with pS2 and TG1f3, but 10-to 100-fold higherilower with monoamine oxidase A and al-antichymotypsin, respectively. The results are in agreement with results obtained by other methods and suggest that an assay based on endogenous gene expression may offer an attractive alternative to other E-SCREEN methods.