The effects of short treatments (7 days) with clomipramine and fluvoxamine on the reactivity to inhalations of 35% CO2/65% O2 were compared in 39 panic patients who had positive responses to 35% CO2 inhalations. A double-blind, randomized, placebo-controlled design was applied. Each patient was given the 35% CO2 challenge on days 0 (before starting treatment), 3, and 7. Patients on placebo did not report any significant changes in their reactivity to 35% CO2 across the three sessions, whereas patients on clomipramine and fluvoxamine reported a significant attenuation of the reactivity on day 7. These results indicate that treatments with clomipramine and fluvoxamine decrease hypersensitivity to 35% CO2 after a few days, suggesting a relevant role of the modulation of CO2 sensitivity by the serotonergic system in antipanic properties of these compounds.