Yohimbine, an alpha 2-adrenergic receptor antagonist that increases noradrenergic function, was administered to 20 healthy subjects and 39 drug-free patients with agoraphobia and panic attacks. Following drug administration, changes in plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), BP, pulse rate, and subjective ratings of feelings and somatic symptoms were examined during a four-hour period. Yohimbine produced significantly greater increases in patient-rated anxiety, nervousness, palpitations, hot and cold flashes, restlessness, tremors, piloerection, and sitting systolic BP in the total patient group compared with healthy subjects. There were significant correlations between the yohimbine-induced rise in plasma MHPG level and patient-rated anxiety and nervousness and the frequency of reported panic attacks. Patients experiencing frequent panic attacks (greater than 2.5 per week) had a significantly greater plasma MHPG response to yohimbine than the healthy subjects and patients having less frequent panic attacks. These observations support a hypothesis of increased sensitivity to augmented noradrenergic function in anxiety states associated with panic, and they suggest that impaired presynaptic noradrenergic neuronal regulation may exist in patients with frequent panic attacks.