Imidazoline receptors (IR), a novel family of non-adrenergic receptors, are present in brain, especially the limbic system, and platelets among other organs. Their functions include central mediation of blood pressure control and possibly modulation of affective symptomatology. Studies of unipolar depressed patients have revealed consistent up-regulation of the I1 subtype on the platelet. Treatment with cyclic antidepressants is accompanied by down-regulation in responders. Treatment with the non-cyclic bupropion produced similar findings. Studies of human post-mortem brain show changes in depressed subjects but the protein fragments assessed are of different molecular weights than in the platelet. Plasma agmatine is believed to be a putative endogenous ligand for I receptors. Thus, IR may be useful state markers of affective disorders. Copyright © 2001 John Wiley & Sons, Ltd.