The effect of single doses of alprazolam (1.5 mg) and yohimbine (30 mg) and alprazolam and yohimbine given together on plasma free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), cortisol, blood pressure, and subjective behavioral ratings was studied in eight healthy subjects. In comparison to placebo, alprazolam significantly reduced plasma MHPG and cortisol, systolic and diastolic blood pressure, and increased subjective ratings of drowsiness and mellow. Yohimbine and the alprazolam-yohimbine combination significantly increased plasma free MHPG. Concomitant yohimbine administration antagonized the effects of alprazolam on blood pressure and attenuated alprazolam-induced changes in cortisol and subjective ratings. The ability of alprazolam to decrease plasma MHPG and blood pressure contrasts with previously reported effects of diazepam. The implications of the findings of the present investigation to the postulated role of brain noradrenergic function in the etiology of panic anxiety and the therapeutic mechanism of action of antipanic treatment are discussed.