Interstrain mice variability in response to antidepressant drugs has been reported in the most commonly utilized behavioural animal models of depression: the tail suspension test (TST) and the forced swimming test (FST). The behaviour of mice was examined in both tests for screening various antidepressants with different biochemical mechanism of action. Previous studies have revealed that drug sensitivity depends on the strain and test used. Swiss mice is the most sensitive strain to detect serotonin and/or noradrenaline antidepressants whereas C57BL/6J was the only strain sensitive to bupropion (dopaminergic agent) using the FST. In the TST, all antidepressants studied decreased the immobility time in Swiss and C57BL/6J strains. Detection of an antidepressant-like activity could be performed using only one test (TST with Swiss mice or FST with Swiss and C57Bl/6 Rj mice), but both tests are necessary to conclude on the mechanism of action.