Vasoactive intestinal peptide (VIP) is an important mediator of development during the neural tube closure period of embryogenesis and may regulate, in part, the expression of activity-dependent neuroprotective protein (ADNP), which is essential for neural tube closure and embryogenesis. To evaluate the impact of VIP expression in vivo on ADNP and the related protein ADNP2 the current study examined gene expression in adult wild-type (VIP +/+) and VIP null (VIP -/-) offspring of VIP deficient mothers (VIP+/-) comparing them to wild-type offspring of wild-type mothers. Quantitative real time polymerase chain reaction (PCR), using an ABI Prisma cycler revealed regionally specific reductions of ADNP mRNA in the brains of VIP null mice compared with the brains of wild-type offspring of a wild-type mother. ADNP was significantly reduced in the cortex and hypothalamus of VIP null mice, but not in the hippocampus or thalamus. ADNP2 exhibited a similar pattern but reached a statistically significant reduction only in the hypothalamus. The mRNA for ADNP and ADNP2 also tended to be reduced in the cortex and hippocampus of the wild-type littermates of the VIP null mice, indicating that the VIP genotype of the mother may have had an impact on the ADNP expression of her offspring, regardless of their own VIP genotype. These results showed that VIP regulated brain ADNP expression in a regionally specific manner and indicated that both maternal and offspring VIP genotype may influence ADNP expression in the brain.