Anxiety and depression are the most commonly occurring psychiatric disorders with serotonin-selective reuptake inhibitors (SRIs) often being prescribed to treat symptoms of these disorders. However, SRIs and other current antidepressant therapies do not work effectively in as many as 40% of patients and different drugs are usually tried over the course of weeks to months, sometimes without success. In order to discover truly innovative treatments to help patients that respond poorly to current drug therapies, the underlying genetic and environmental causes of anxiety and depression must first be understood. Current approaches rely heavily on targeted gene strategies to determine the functions of specific genes and gene-environment interactions already suspected of playing a role in imparting vulnerability to depression and anxiety disorders. A different approach involves using recombinant inbred strains to identify new gene targets for investigation. Toward that goal, we studied strains 11 and 31 B×D male mice to characterize further differences in anxiety-related behavior. These strains were chosen because they appear to show low and high anxiety-like behavior, respectively (Holmes et al. unpublished). Behavior was evaluated using the elevated plus maze (EPM) and the open field. Strain 11 mice showed longer latencies to enter a first arm, fewer open arms entries and shorter time in the open arms. They also showed fewer closed arms entries, however, they spent the same amount of time in the closed arms as strain 31 mice. Thus total arm entries were significantly decreased in strain 11 versus strain 31, while total arm time was unchanged. Total distance traveled in the open field was significantly decreased in strain 11 suggesting that some of the differences in behavior in the EPM may be due to overall decreases in activity levels in strain 11. With a clearer picture of how anxiety-related behavior differs across a variety recombinant inbred strains, individual strains can be chosen for further quantitative trait loci mapping.