Noradrenergic function was studied in patients with primary affective disorder and other tricyclic-responsive disorders including obsessive-compulsive disorder, anorexia nervosa and panic attack/agoraphobia in medication-free states. Pre-synaptic noradrenergic activity was assessed by assaying plasma concentrations of norepinephrine (NE) and its metabolite 3-methoxy,4-hydroxyphenylglycol (MHPG). Noradrenergic receptor responsiveness was evaluated by measuring plasma growth hormone (GH), MHPG, and NE responses to clonidine. Binding of tritiated dihydroergocriptine (3H-DHE) and biochemical responsiveness of alpha 2-adrenergic receptors were measured in platelet preparations. These studies suggest that noradrenergic activity may be altered in several tricyclic-responsive disorders and are consistent with the possibility that tricyclic antidepressants may serve to stabilize a dysregulated noradrenergic system in patients from several diagnostic categories.