As reported previously, berberine, the main component extracted from Coptis rhizome and Phellodendron, has potential as a contraceptive for animals since berberine has a strong inhibitory effect on the in vitro development of mouse zygotes and on fetal development in vivo. The present study was undertaken to examine the effect of berberine treatment on the reversibility of the development of zygotes and gametes, and on the fertilization and subsequent development in the mouse. The reversibility of the berberine-induced inhibition of the development of mouse zygotes was dependent on the concentration used and treatment period. Berberine treatment did not inhibit the fertilizing capacity of epididymal spermatozoa and the fertilizability of oocytes at the second metaphase stage. The present study demonstrated that in vitro development of mouse zygotes is about 100 times more sensitive to berberine than the in vitro growth of mouse fetal fibroblast cells. The high stability of berberine at low temperatures for at least for 12 months and the high sensitivity of preimplantation embryos to berberine is useful information when considering the administration of berberine to females as a contraceptive.