The effects of various alpha 2 adrenoceptor agonists on forced swimming-induced despair behaviour were studied in mice. Clonidine, B-HT 920 and guanfacine significantly prolonged the total immobility duration. Clonidine-induced behavioural despair was antagonized by prior treatment with yohimbine. The tricyclic antidepressants imipramine, desipramine, trimipramine, amitriptyline, nortriptyline and doxepin, the MAO inhibitor tranylcypromine, and the antimanic agent lithium reversed clonidine-induced behavioural despair. Chronic treatment with imipramine evoked more pronounced reversal as compared to acute treatment. Amphetamine, a psychostimulant, inhibited clonidine-induced enhancement of immobility duration but diazepam, a skeletal muscle relaxant was without any effect. On the other hand, adenosine showed potentiation of the submaximal response of clonidine. These observations suggest that clonidine-induced behavioural despair is probably mediated through its presynaptic action on alpha 2 adrenoceptors, resulting in reduced central noradrenergic outflow. The present data proposes a simple test system to induce depression-like syndrome in animals, sensitive to antidepressant therapy.