Panic disorder (PD) and social phobia (SP) share many clinical, demographic and biological characteristics. To investigate the relationships between the two disorders, the responses to inhalation of a 35% carbon-dioxide (CO2) and 65% oxygen (O2) gas mixture were assessed. Sixteen patients with PD, 16 patients with SP, 13 patients with both SP and PD, seven patients with SP who experienced sporadic unexpected panic attacks and 16 healthy control subjects inhaled one vital capacity of 35% CO2 or compressed air. A double-blind, randomized, crossover design was used. PD patients and SP patients showed similar anxiogenic reactions to 35% CO2, both stronger than seen in control subjects. Patients with both disorders and SP patients with sporadic unexpected panic attacks reacted similarly to subjects with PD or SP alone. These results suggest that PD and SP share a common hypersensitivity to CO2 and thus might belong to the same spectrum of vulnerability.