Psychologic stressors are less potent stimuli of the HPA axis in humans than physical stressors, but they can cause mild changes in acute ACTH and cortisol production. These changes, however, are generally not of sufficient magnitude or duration to cause measurable changes in UFC excretion. Furthermore, chronic stress leads to an attenuation of the HPA axis response. This basic knowledge concerning psychologic stress helps explain the reason why patients with uncomplicated anxiety/panic disorder, a condition involving similar symptoms, do not demonstrate UFC abnormalities. Panic disorder, when accompanied by depression, however, is associated with an increase in UFC excretion which is probably more related to the depression than the panic state. Interestingly, panic disorder, when accompanied by agoraphobia, also shows an elevation in UFC levels which makes it endocrinologically distinct from uncomplicated panic disorder. The reason for this is unclear. Treatment of the panic disorder with benzodiazepines does not further lower the UFC levels in patients with uncomplicated panic disorder despite clinical improvement, but it does lower UFC levels into the normal range in those with concurrent depression and agoraphobia. Alteration in the UFC level with treatment is only partially related to clinical improvement.