Silastic capsules are frequently used to study the physiologic effects of estrogen exposure in animal models. The Office of Laboratory Animal Welfare requires the sterilization of nonpharmaceutical-grade compounds before use. We compared 2 commonly used terminal sterilization methods-ionizing radiation (IR) and ethylene oxide (EO)-for their utility in sterilizing silastic capsules containing 0.05 or 0.1 mg 17β-estradiol (E2). E2-specific ELISA demonstrated that serum estrogen levels did not differ between mice implanted with 0.05-mg E2 capsules that were sterilized with IR or EO and those implanted with nonsterilized capsules. Likewise, mammary gland morphology and progesterone receptor expression and proliferation in mammary epithelium were similar among mice treated with E2 capsules, regardless of sterilization method, and pregnant day 15 mice. In addition, IR-sterilized 0.1-mg E2 pellets provided high serum E2. We conclude that neither ionizing radiation nor ethylene oxide degraded E2 or the cellulose matrix, suggesting that these methods of sterilization are appropriate to provide effective sterile hormone capsules for animal research.