A search for susceptibility genes for psychiatric illness may benefit from recent advances in mouse molecular genetics. Molecular and phenotypic characterization of single gene mutations in mice with anomalies in neurophysiological or neurodevelopmental processes, disrupted in a psychiatric disease, can reveal new insights into the pathways that underlie these genetically complex illnesses. However, in the case of many psychiatric disorders such as autism and schizophrenia, the exact nature of these neurophysiological or neurodevelopmental processes is not known. For example, nothing is known about the molecular pathology underlying impaired social behavior, a prominent feature of both autism and schizophrenia. In this review we discuss published reports on genetic and pharmacological studies of social behavior in mice. We argue that paradigms for studies of the genetics and neurobiological origins of social interactions in mice are amenable to gene- and phenotype-based mutagenesis screens and that identification of a core set of genes that underlie social behavior in mice may provide important clues for our understanding of some aspects of autism and schizophrenia.