The effect of manipulations aimed at modifying the function of the 5-HT system has been reviewed. 5-HT uptake inhibitors are devoid of any activity in rats and induce an anti-immobility effect in mice. The so-called 5-HT1A agonists reduce the immobility time with some differences in mice and rats, mice being less sensitive. None of the procedure aimed at reducing 5-HT function reduced immobility time. Therefore, the 5-HT system does not play a tonic role in animals performing the forced swimming test. The involvement of possible brain regions mediating the anti-immobility effects of 5-HT mimetic drugs has been discussed.