Genetic alterations can unpredictably compromise the wellbeing of animals. More or less harmful phenotypes can appear in animals used in research projects, even when they are not subjected to experimental procedures.The severity classification of animal procedures has become an important issue since the implementation of the EU Directive 2010/63/EU on the protection of animals used for scientific purposes. According to this Directive, the breeding and maintenance of genetically altered (GA) animals which are likely to develop a harmful phenotype have to be authorized. However, determination of the degree of severity is challenging, due to the large variety of phenotypes displayed by GA animals. This thesis describes the development and field testing of guidelines for severity assessment and classification of GA rodents. Focusing on basic welfare assessment and severity classification, a list of symptoms is provided for classification as non-harmful, mild, moderate or severe. Corresponding monitoring and refinement strategies, as well as specific housing requirements, have been compiled and are strongly recommended to improve current breeding procedures and husbandry conditions. The presented document serves as a guide for determining the degree of severity for an observed phenotype. The aim of the work has been to support scientists, animal caretakers, animal welfare bodies and competent authorities with this task, and thereby make an important contribution to European harmonization of severity assessment for the growing number of GA rodents. The guidelines will be reviewed regularly and updated as needed.Further steps are necessary to harmonize severity classification across Europe. An efficient exchange of line-specific data is a prerequisite for good animal welfare practices and high scientific quality.