The anxiogenic effects of yohimbine, a specific alpha-2-receptor antagonist were examined by administering 20 mg yohimbine orally to 8 panic patients on placebo treatment, 7 panic patients on alprazolam treatment and 12 controls using a double-blind randomized design, instructions that minimized the expectancy of experiencing a panic attack and two additional structured situations. Yohimbine induced more pronounced increases in anxiety and panicky ratings, norepinephrine secretion, maximum heart rate and high heart rate variability and decreases in skin temperature in panic patients compared with controls. However, possibly owing to an instructional set and experimental design that distracted patients from unpleasant bodily sensations no panic attacks were observed.