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The estrogenic effect of chemicals, including 1-chloro-2,4-dinitrobenzene (CDNB), in the combination with 17β-estradiol (E 2 ) was screened by a reporter gene assay using breast cancer cells (MCF-7). It was found that CDNB stimulated E 2 -induced transcriptional activity of estrogen receptor (ER) and down-regulated both ER protein and mRNA. However, CDNB alone and CDNB metabolite(s) showed no estrogenic activity and no binding activity to ER, suggesting an indirect pathway other than ER. CDNB gave no transcriptional activity for an aryl hydrocarbon receptor (AhR), suggesting no possibility of a pathway through cross-talk between AhR and ER. On the other hand, CDNB enhanced the mitogen activated protein kinase (MAPK) pathway, suggesting estrogenic action via MAPK. These results indicated that CDNB possessed estrogen-like activity in the transcription and regulation of ER though a different pathway from E 2 .