The antiprogesterone RU 486 was utilized to evaluate the possible role of progesterone in ovum maturation, ovulation, fertilization, and embryo cleavage. After gonadotropin treatment, CD-1 mice received the following experimental agents: group 1, an oil vehicle; group 2, 1 mg progesterone; group 3, 1 mg antiprogesterone (RU 486); group 4, 1 mg RU 486 and 1 mg dexamethasone. Each group of animals was injected simultaneously for 2 days (concomitant with human chorionic gonadotropin and the day after coitus). Ova or embryos were obtained on day 1, 2, 3, or 4 after human chorionic gonadotropin by flushing uteri and tubes. No differences were apparent in number of oocytes ovulated, ovum maturation, or number of oocytes progressing to two-cell embryos. However, on day 3 a marked reduction in embryos retrieved from the oviduct and uterus was apparent in the RU 486-treated groups (group 1, 84; group 3.0; group 4, 17) (p less than 0.001). In addition, few cleavage stage embryos were recovered on day 4 in the RU 486-treated groups (group 1, 74; group 2, 70; group 3, 2; group 4, 0) (p less than 0.0001). Freshly ovulated cumulus masses were recovered from the oviducts on day 4 in groups 3 and 4 (coincident with resumption of the estrous cycle). In conclusion, periovulatory RU 486 injections had no effect on nuclear maturation, ovulation, fertilization, or first cleavage division. Progesterone may not have an obligatory role in these processes. However, RU 486 administration did result in a reduced number of embryos retrieved on days 3 and 4 because of either early expulsion or destruction of the embryos.