A previously demonstrated synergistic interaction between diethylstilbestrol (DES) and radiation on rat mammary carcinogenesis was extended to another estrogen, 17-ethinylestradiol (EE2). These newly reported results with EE2 demonstrated that the previously reported synergistic interaction between DES and radiation is not confined to just DES. Instead, these new results implied that the synergistic interaction is a synergistic interaction between the estrogenic activity of DES and radiation on rat mammary carcinogenesis. Female inbred ACI rats were used. By the end of the experiment, no neoplasia was detected in rats bearing cholesterol pellets, with and without X-ray exposure. No significant tumor data were obtained from rats treated with 0.1 me EE2, with and without X-rays. Approximately 50% of the rats treated with DES and approximately 90% of the rats treated with 1 mg EE2 had 1 or more mammary adenocarcinomas (MAC). X-rays synergistically increased the number of MAC per rat in the groups implanted with DES or 1 mg EE2. X-rays also increased the trend toward earlier increased incidence of rats with MAC as compared to rats treated with estrogens only. All rats treated with DES and 1 mg EE2 had pituitary tumors. The mean weight of the pituitary tumors in the groups treated with 1 mg EE2 was approximately 1.5 times that of the groups treated with DES. Mean terminal plasma prolactin levels for rats treated with 1 mg EE2 or DES were, respectively, 17.5 and 9.5 times control values.