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Embryos were extracted on GD 12 and genotyped for both<jats:italic>Pax3<\/jats:italic>and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Arsenite treatment was a significant contributor to both exencephaly and spina bifida. Advanced maternal age resulted in a high exencephaly rate in<jats:italic>Sp<\/jats:italic>\/<jats:italic>Sp<\/jats:italic>female embryos (but not other genotypes) and a high overall resorption rate. Arsenite treatment and advanced maternal age resulted in elevated sex ratios (male:female) for heterozygous and wild\u2010type embryos. The sex ratio was highest for wild\u2010type embryos and was lowered as the number of mutant<jats:italic>Pax3<\/jats:italic>alleles increased. The sex ratio was not significantly different from 1.0 for splotch homozygotes. Control litters had spina bifida rates that were 95% in homozygous, 6% in heterozygous, and 0% in wild\u2010type embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>If arsenite produces exencephaly by inactivating the Pax3 protein, then the fact that the exencephaly rate was increased in<jats:italic>Sp<\/jats:italic>\/<jats:italic>Sp<\/jats:italic>embryos with no functional Pax3 indicates that arsenite may either induce this defect through additional pathways, or may alter the response via modifier genes. Genetic and environmental factors contributed to the determination of murine sex ratios, with female embryos being more susceptible to loss. 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