In behavior genetics, behavioral patterns of mouse genotypes, such as inbred strains, crosses, and knockouts, are characterized and compared to associate them with particular gene loci. Such genotype differences, however, are usually established in singlelaboratory experiments, and questions have been raised regarding the replicability of the results in other laboratories. A recent multilaboratory experiment found significant laboratory effects and genotype ؋ laboratory interactions even after rigorous standardization, raising the concern that results are idiosyncratic to a particular laboratory. This finding may be regarded by some critics as a serious shortcoming in behavior genetics. A different strategy is offered here: (i) recognize that even after investing much effort in identifying and eliminating causes for laboratory differences, genotype ؋ laboratory interaction is an unavoidable fact of life. (ii) Incorporate this understanding into the statistical analysis of multilaboratory experiments using the mixed model. Such a statistical approach sets a higher benchmark for finding significant genotype differences. (iii) Develop behavioral assays and endpoints that are able to discriminate genetic differences even over the background of the interaction. (iv) Use the publicly available multilaboratory results in single-laboratory experiments. We use software-based strategy for exploring exploration (SEE) to analyze the open-field behavior in eight genotypes across three laboratories. Our results demonstrate that replicable behavioral measures can be practically established. Even though we address the replicability problem in behavioral genetics, our strategy is also applicable in other areas where concern about replicability has been raised.across-laboratory replicability ͉ mixed-model ANOVA ͉ open-field behavior I n behavior genetics, behavior patterns of standardized mouse genotypes, such as inbred strains or knockouts, are characterized to associate them with particular gene loci. The need for such characterization, referred to as behavioral phenotyping, has prompted the design of behavioral test batteries for mice (1-3). A practical problem well known to most experimenters in the field, however, is that it can be difficult to replicate behavioral phenotyping results in a different laboratory. This replicability problem was largely ignored until brought to light in 1999 by Crabbe, Wahlsten, and Dudek (3). In this pioneering study they conducted an experiment concurrently in three laboratories, comparing eight genotypes by using seven standard behavioral characteristics (endpoints) in a well coordinated study closely following identical protocols. Their main positive finding was that large genotype differences were demonstrated in all studied endpoints. On the negative side they found significant differences between laboratories across all genotypes in many endpoints. Although the difficulties raised by such significant laboratory effects can be overcome by running a common genotype as a local control, they ...