Yohimbine, an alpha 2 adrenoreceptor antagonist, enhances norepinephrine (NE) release and increases sympathetic activity. We examined the behavioral, peripheral sympathetic and adrenocortical responses to oral yohimbine in seven healthy controls and 11 patients diagnosed with agoraphobia with panic attacks (PD). Patients did not differ in baseline cardiovascular or neuroendocrine measures from controls despite significantly higher baseline anxiety ratings. Placebo caused no changes in baseline-corrected behavioral, cardiovascular or neurochemical responses in either group. Yohimbine induced a panic episode in six PD patients, but no controls. PD patients had significantly higher severity scores of autonomic anxiety symptoms. Yohimbine significantly raised systolic blood pressure (F = 3.07, P < 0.03), plasma NE levels (F = 12.11, P < 0.00) and cortisol levels (F = 4.82, P < 0.02), but had no effect on epinephrine levels. NE responses were similar in both groups, but patients had higher cortisol responses to yohimbine than controls (F = 7.14, P < 0.01). The correlational pattern between behavioral ratings and neuroendocrine responses in patients was opposite to that observed in controls. Despite similar increases in plasma NE levels between PD patients and healthy controls, PD patients had greater anxiogenic, cardiovascular and cortisol responses to yohimbine. Enhanced post-synaptic adrenoreceptor sensitivity may explain the noradrenergic dysregulation found in panic disorder.