The nervous system is one of the most complicated organ systems in invertebrates and vertebrates. Down syndrome cell adhesion molecule (DSCAM) of the immunoglobulin (Ig) superfamily is expressed widely in the nervous system during embryonic development. Previous studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching, dendritic tiling and cell spacing. However, the function of the mammalian DSCAM gene in the formation of the nervous system remains unclear. Here, we show that Dscam ( del17 ) mutant mice exhibit severe hydrocephalus, decreased motor function and impaired motor learning ability. Our data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system.