Tricyclic antidepressants vary in their capacity to cause psychomotor activation, to relieve agitated depressive states, and to cause sedation and hypotension. We have quantified relative potencies of tricyclic antidepressants in competing for the binding of ³H-labeled WB-4101 to α-noradrenergic receptor sites in rat brain membranes. Affinities of tricyclic drugs for α-noradrenergic receptor sites in the brain correlate well with the capacity of these agents to relieve psychomotor agitation and to induce sedation and hypotension; these affinities also correlate inversely with tendencies to elicit psychomotor activation.