The effect of 4-hydroxytamoxifen (4OH-TAM), the potent anti-estrogenic metabolite of tamoxifen, on the radiosensitivity of MCF-7 cells irradiated in vitro was determined. Radiation dose response curves were generated for MCF-7 cells maintained and irradiated in phenol red-free medium containing 10(-10) M estradiol (E2) with or without 10(-7) M 4OH-TAM. Immediately after irradiation cells were transferred to medium containing 10(-10) ME2 supplemented with bovine serum to stimulate colony formation. Estradiol-stimulated cell proliferation was inhibited by 10(-7) M 4OH-TAM, but radiation sensitivity was not significantly altered (p > 0.3). Continued incubation in the absence of E2 for an additional 24 hours after irradiation likewise failed to alter the radiosensitivity of 4OH-TAM-treated MCF-7 cells. These studies indicate that growth-inhibitory concentrations of the anti-estrogen 4OH-TAM do not modify the in vitro radiation sensitivity of this line of human breast carcinoma cells.