Caffeine administered to pregnant mice during germinative neuroepithelium preparation (embryonic days 8-10) dramatically accelerated primitive neuroepithelium evagination into telencephalic vesicles, versus age-matched controls. This histologically-documented, dose-dependent effect seemed reversible during subsequent neuronal migration if caffeine exposure was discontinued. Our in vivo model provides a new tool for studying telencephalic symmetry acquisition and for identifying genes potentially involved in holoprosencephaly, a developmental disorder characterized by defective telencephalic vesicle formation.