Complementary to the 'gene-driven' analysis of gene function, 'phenotype-driven' approaches can be performed and may be equally important. Despite the current availability of a long list of mouse mutants, there remains an appreciable need for behavioural phenotypes in mouse models permitting to learn more about the aetiology of psychiatric disorders. This lack can be compensated by phenotype-driven ethyl-nitrosourea (ENU)-mutagenesis programs which aim at identifying novel phenotypes without any a priori assumptions, thus, representing a unique possibility to create novel animal models which approximate the underlying genetic aetiology. The power of mouse mutagenesis critically depends on the phenotyping procedures performed. In the case of ENU-mutants, behavioural phenotyping is especially challenging, as behavioural profiles have to be identified in single individuals. For high-throughput screening, approaches have been made to establish standardised screening protocols including a combination of well-validated, easy to perform behavioural tests. Different strategies are being introduced, which are used in ENU-mutagenesis screens to identify behavioural mutants representing possible endophenotypes of psychiatric diseases.