Fetal alcohol syndrome (FAS) is a congenital anomaly attributable to prenatal maternal excessive intake of ethanol. The authors made a mammalian model of FAS by culturing mouse embryos with high ethanol for embryonic day 7.8 to 9.5 in the whole embryo culture system. The embryos exposed to high ethanol were smaller and less advanced in development than were the embryos in the control group and showed craniofacial abnormalities, such as a fusion defect of the neural tube. The expression patterns of CRABP-I and AP-2 as markers of the neural crest cells were mostly unchanged in the in situ hybridization. However, the density and area of the expression were decreased, possibly because of the death of the neural crest cells. The expression patterns of the Sonic hedgehog signaling cascade genes (Shh, Ptc-1 and Gli-1) were mostly unchanged in the in situ hybridization, but the quantitative expressions of Ptc-1 and Gli-1 were increased in real-time reverse transcriptase-polymerase chain reaction analyses, quite contrary to the findings of a previous study using chick embryos. These findings suggest Shh signaling also is involved in the pathogenesis of FAS in mammalian embryo, but in a mode different from that in the chick embryo.