Using animals for research is a privilege granted by society to scientists on the explicit understanding that such use will provide significant new knowledge, and no unnecessary harm will be imposed on the animals. However, a high prevalence of abnormal behaviour and other signs of distress in animals housed under standard laboratory conditions, and poor reproducibility of experimental results, suggest that current practice needs to improve to guarantee sound science. Recently we have shown in mice that standard housing conditions may interfere with behavioural control mechanisms expressed as overt behavioural disorders. These findings question both the animals’ welfare and the validity of research conducted with them. Furthermore, we have shown that current practice of standardisation may compromise the external validity of experimental results, resulting in poor reproducibility and spurious results. The overall hypothesis underlying this project is that both impaired welfare and poor reproducibility are caused by a failure to account for fundamental principles of phenotypic plasticity, whereby animal welfare is impaired when the animals’ adaptive plasticity is overtaxed, and reproducibility is compromised when phenotypic variation is standardised away. Based on this framework, the project, therefore, aims to systematically assess environmental effects on the welfare of laboratory animals and on the validity and reproducibility of animal experiments, using the mouse as a model species. The new results should greatly advance our understanding of environmental effects on the quality of life of laboratory animals and on the quality of science conducted with them. They should help to reconcile laboratory animal science with the biological principles of phenotypic plasticity, thereby providing significant new knowledge for effective Refinement of animal research. This should benefit the science as well as the animals in the best meaning of the 3R concept.