AbstractThe effect of tamoxifen on the radiosensitivity of an estrogen receptor positive (ER+) and an estrogen receptor negative (ER−) breast carcinoma cell line was studied in vitro. Tamoxifen concentrations of 1 and 5 μM inhibited the proliferation of ER+ MCF‐7 cells but had little effect on the growth of ER− MDA‐MB‐231. A 48 hr incubation in tamoxifen increased the proportion of G0/G1MCF‐7 cells, but minimally altered the cell cycle kinetics of MDA‐MB‐231 cells. Tamoxifen resulted in a small but significant increase in the mean inactivation dose of subconfluent cultures of the ER+ cells but had no effect on the ER− cells. The predominant change for MCF‐7 cells was a decrease in the linear damage coefficient, alpha. This was not associated with any enhanced capacity to recover from split radiation fractions. There was no difference in radiosensitivity comparing irradiated log‐phase to immediately plated plateau‐phase cells. However, 24 hr delayed plating of irradiated plateau‐phase cells resulted in decreased radiosensitivity of a magnitude comparable to that seen with tamoxifen. Quantitation of DNA strand fragmentation revealed no difference in the amount of single or double strand break induction nor the kinetics of strand break repair for cultures irradiated with or without tamoxifen. We conclude that tamoxifen results in a small decrease in the radiosensitivity of proliferating hormone responsive breast carcinoma cells and this effect appears to be most related to delay in cycle progression after release from tamoxifen inhibiti