Abstract. Rationale: The C57BL/6 is one of the most widely used mouse strains in behavioral, pharmacological, and genetic research but little is known about their response on tests for antidepressant drugs. Objectives: The behavior of C57BL/6 mice, and mice from other strains, was examined in the tail suspension test (TST), a common behavioral test used for the screening of antidepressant compounds. Methods: C57BL/6J mice from the Jackson Laboratory, C57BL/6N mice from Harlan, A/J, 129-SV-ter and DBA/2 mice were tested under baseline conditions in the TST. Results: The majority of the C57BL/6 mice from the Jackson Laboratory tested in this paradigm (70%) climbed up their tails during the 6-min test session. C57BL/6 mice obtained from Harlan (35%) also demonstrated this climbing behavior, suggesting that it is not specific to mice from a particular supplier. Other strains (A/J 18%), 129-SV-ter (0%) and DBA/2 (0%) mice) showed less propensity for tail climbing. Conclusions: The occurrence of this behavior is an important consideration when testing antidepressant drugs or the effects of stress using the TST with inbred mouse strains, especially those from the C57BL/6 strain.