Background: Due to the increasingly common use of endocrine therapy in adjuvant and palliative therapy of breast cancer, a significant number of patients will be treated with radiation therapy and Tamoxifen (TMX) at the same time. Methods: MCF-7 breast cancer cells, cultured by standard methods, were treated with varying doses of TMX or estrogen (ES) and/or graded doses of X-rays. The effects were measured by a clono-genic survival assay. Results: We found a marked decrease in the radiosensitivity of MCF-7 cells which were treated with TMX. This effect was time- and concentration-dependent, with a maximum at a 72-hour incubation. Treatment of the cells with estrogen (ES) increased their radiosensitivity at very high ES doses only. Conclusion: For patients treated with radiotherapy and TMX simultaneously, a negative effect can not be excluded.