ABSTRACT‐A model for the development of agoraphobia with panic attacks is proposed. The initiating clinical manifestation is the sudden appearance of spontaneous panic. The inter‐panic chronic anxiety may have several components: i.e. conditioning, increasing autonomic distress, and sensitization to the panic leading to avoidance. The illness course is quite variable but usually chronic. The spontaneous panic is blocked by imipramine with primary pharmacological anti‐panic effects. However, no direct effect of imipramine upon either anticipatory anxiety or avoidance behaviour is hypothesized. Among the psychotherapies, direct in vivo exposure mobilizes the patient more rapidly than office based therapy. Our data are consonant with the theory that the avoidances of agoraphobia are secondary to spontaneous panic attacks, and that the primary benefits of imipramine and exposure therapy are in their respective effects on panic and avoidance. Moreover, laboratory challenge studies, brain imaging studies, and genetic studies all point to a biological diathesis for panic dis