Colony-forming ability after exposure to ionizing irradiation was compared for proliferating hormone response MCF-7 breast carcinoma cells and cells whose growth was inhibited by tamoxifen or 17B-estradiol. As compared with controls (Do = 1.20 Gy, n = 3.1), cells in 1 microM or 5 microM tamoxifen were less radiosensitive (Do = 1.20 Gy, n = 7.0; Do = 1.22 Gy, n = 7.0, respectively) with the predominant effect being a widened shoulder on the survival curve. This protective effect could be abolished by co-incubation of 5 microM tamoxifen with 100 nM 17B-estradiol (Do = 1.30 Gy, n = 2.6; Do = 1.20 Gy, n = 2.6, respectively). The decrease in radiosensitivity induced by tamoxifen was similar to that seen when replating of irradiated plateau-phase cultures was delayed for 24 h (Do = 1.30 Gy, n = 6.0). In contrast, when proliferation of MCF-7 cultures was inhibited by 10 microM 17B-estradiol, radiosensitivity was increased with a markedly diminished survival curve shoulder (Do = 1.40 Gy, n = 1.0). Different hormonal manipulations of cycling human breast carcinoma cells may have profound but disparate effects on radiosensitivity such that tamoxifen and estrogens may serve as useful agents with which to study the biochemical mechanisms of repair.