Over 90% of Rett syndrome (RTT) cases have a mutation in the X-linked gene encoding methyl CpG binding-protein 2 (MeCP2). A mouse model that reprises clinical manifestations of the disease would be valuable for examining disease mechanisms. Here, we characterize physical and behavioral measures, as well as brain region volumes in young adult mice that have mutations in mouse methyl CpG binding-protein 2 gene (Mecp2) to serve as a baseline for other studies. Hemizygous males, which produce no functional protein, exhibit hypoactivity and abnormalities in locomotion, stereotypies, and anxiety reminiscent of the clinical condition. The mutant males also exhibit cognitive deficits in fear conditioning and object recognition relative to wildtypes. Volumetric analyses of male brains revealed a 25% reduction in whole brain volume in mutants relative to wildtypes; regional differences were also apparent. Mutants had decreased volumes in three specific brain regions: the amygdala (39%), hippocampus (21%), and striatum (29%). Heterozygous females, which produce varying amounts of functional protein, displayed a less severe behavioral phenotype. The mutant females exhibit abnormalities in locomotion, anxiety measures, and cognitive deficits in object recognition in an open field. This study provides the first evidence that the abnormal motor and cognitive behavioral phenotype in Mecp2 mice is consistent with specific volume reductions in brain regions associated with these behaviors, and shows how these data parallel the human condition. The Mecp2 mutant mice provide a very good model in which to examine molecular and behavioral mechanisms, as well as potential therapeutic interventions in RTT.