NMDA receptor (NMDAR) hypofunction theory of schizophrenia has been assessed in rodents with pharmacological intervention and global knockout strategy of NMDAR blockade. However, these manipulations of NMDAR function have been relatively coarse, affecting all NMDA receptors throughout the brain. Here we tested the effects of eliminating NMDA receptors in about half the interneurons located in the cortex and the hippocampus in early postnatal development by engineering “conditional knockout” mice. Remarkably, the mutant mice produced a variety of schizophrenia-related phenotypes.