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BACKGROUND: It has been demonstrated that 2-Methoxyestradiol (2-ME), one of the estrogen metabolites, induces apoptosis in many different tumor cell lines. In the present study, the effects of 2-ME on human cervical cancer HeLaS3 cells and on normal cervical epithelial cells were evaluated. MATERIALS AND METHODS: Acridine orange staining, DNA fragmentation arrays and flow cytometry were used to measure the apoptosis and cell cycle progression. In addition, the effect of 2-ME on expression of iNOS was measured by Western blot. RESULTS: 2-ME inhibited the growth of HeLaS3 cells. This growth inhibition was accompanied by apoptosis and G2/M cell cycle arrest. 2-ME increased the expression of iNOS in parallel with apoptosis. Moreover, apoptosis was prevented by the iNOS inhibitor 1400W. 2-ME treatment resulted in a slight increase of the G2/M population, but no apoptosis, in normal cervical epithelial cells. There was no synergetic effect between E2 and 2-ME. CONCLUSION: 2-ME induced apoptosis via the iNOS pathway and caused G2/M cell cycle arrest in human cervical cancer HeLaS3 cells, but showed only slight effects on normal cervical epithelial cells. These data suggest that 2-ME might be an adjuvant agent in the treatment of cervical cancer.