Previously, with the administration of antidepressant drugs, it has been demonstrated that the rat model of clinical depression, known as the reduction of submissive behavior model (RSBM), has considerable validity. The present study is an attempt to extend the model to mice. Several antidepressant drugs as well as a number of non-antidepressant agents were administered to mice that had been identified as submissive in a behavioral testing situation. Imipramine, desipramine, amoxapine and fluoxetine, representing three different classes of antidepressant drugs, were each able to increase competitive behavior in submissive mice and to decrease the dominance level between dominant and submissive mice in the behavioral tests. The stimulant amphetamine also reduced submissive behavior while yohimbine (also a stimulant), and the antianxiety agent diazepam had no such effect. The neuroleptic drug thiothixen had antidepressant-like effect on submissive C57BL/6J mice behavior. We conclude that like the rat model of depression from which it was developed, the mouse model responds to various antidepressants as predicted and thus may serve as a potential model of clinical depression.