It is widely believed that environmental standardization is the best way to guarantee reproducible results in animal experiments. However, mounting evidence indicates that even subtle differences in laboratory or test conditions can lead to conflicting test outcomes. Because experimental treatments may interact with environmental conditions, experiments conducted under highly standardized conditions may reveal local 'truths' with little external validity. We review this hypothesis here and present a proof of principle based on data from a multilaboratory study on behavioral differences between inbred mouse strains. Our findings suggest that environmental standardization is a cause of, rather than a cure for, poor reproducibility of experimental outcomes. Environmental standardization can contribute to spurious and conflicting findings in the literature and unnecessary animal use. This conclusion calls for research into practicable and effective ways of systematic environmental heterogenization to attenuate these scientific, economic and ethical costs.