The effects of short treatment (7 days) with the tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors paroxetine and sertraline on the reactivity to inhalation of 35% CO2/65% O2 were compared in 70 panic patients who had positive responses to 35% CO2 inhalations. A double-blind, random, placebo-controlled design was applied. Each patient was given the 35% CO2 challenge on days 0 (before starting the treatment), 3, and 7. In the placebo group, there were no significant changes in the reactivity to 35% CO2 in the three sessions whereas there were significant similar reductions of reactivity to 35% CO2 in all three drug-treated groups. These results confirm the good reproducibility of 35% CO2 reactivity and the negligible effects of placebo on reactivity to CO2 and suggest that short treatments with imipramine, paroxetine, and sertraline decrease reactivity to 35% CO2, possibly as an expression of their antipanic properties.