To study the role of various genes in epidermal development, it is ideal to be able to inactivate their expression in utero at different stages of development. To determine whether RU486 could induce Cre-mediated gene deletion in utero, 100 µg/kg RU486 was injected into pregnant K5.CrePR1 mice bred with ROSA26 mice on day 14.5 of pregnancy. At this stage of gestation, hair follicles are just beginning to form. Progesterone was also injected into these mice at a dose of 0.5 mg/mouse daily to prevent abortion that is potentially induced by RU486. Small pieces of skin were biopsied from the pups after birth and stained with X-gal. β-Gal expression was detected uniformly in bigenic mouse epidermis and hair follicles, but not in the skin of monogenic (ROSA26 or K5.CrePR1) littermates, or the skin of bigenic mice delivered by a mother treated with sesame oil (vehicle control). Furthermore, the skin of CrePR1 or bigenic mice appeared normal (by gross and microscopic examination) after exposure to RU486 in utero. Therefore, this system provides a useful tool for inactivating genes in the epidermis and hair follicles at specific stages of development.