1 Clonidine inhibition of the acoustic startle reflex in the rat was used as a behavioural measure of alpha 2-adrenoceptor sensitivity following acute or chronic administration of tricyclic antidepressants. 2 Chronic (14 day) administration of desipramine (10 mg/kg, i.p.) attenuated the depressant effect of clonidine (20 or 40 microgram/kg) on the startle reflex. 3 No change in response to clonidine was obtained after chronic treatment with two other tricyclic antidepressants, amitriptyline (10 mg/kg) or iprindole (5 mg/kg). 4 Acute administration of these tricyclics (1 h) did not modify the effect of clonidine on startle. 5 It is suggested that the development of alpha 2-adrenoceptor subsensitivity produced by chronic tricyclics may be unique to those compounds, such as desipramine, which are active in blocking the uptake of noradrenaline.