The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious like than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxietyrelated genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments.Keywords: Anxiety, gene-environment interaction, inbred rats, laboratory environment, Lewis, SHR During the past decade, massive and systematic behavioral testing of multiple strains of laboratory rodents became a key step in neuroscience research, particularly in the field of behavior genetics. When populations of animals developed through inbreeding, selective breeding, transgenesis or gene targeting started to be characterized, it became evident that behavioral data from different laboratories were often not reproducible. Such discrepancies could result not only from differences in the genetic background of the animals but also from variations in the testing and/or laboratory environments (1999) has shown that major efforts to standardize both the test situation and the rearing environment do not guarantee the consistency of results across laboratories. For example, the mouse strains A/J and 129/SvEvTac, when compared to each other, displayed either higher or lower locomotor response to cocaine, depending on the laboratory where they were tested, in spite of environmental factors having been rigorously controlled. On the one hand, these data revealed that subtle, uncontrollable environmental variations between and within laboratories can influence behavior genetic studies. On the other hand, the effects of s...