OBJECTIVE: The DSM-III-R anxiety disorders section includes both panic disorder and obsessive-compulsive disorder. To evaluate the relationship between these two disorders, subject responses to inhalation of a 35% CO2 and 65% O2 mixture were assessed. METHODS: Twenty-three patients with panic disorder, 23 with obsessive-compulsive disorder, 12 with both obsessive-compulsive and panic disorder, and 23 healthy comparison subjects were given a single vital capacity inhalation of 35% CO2 and 65% O2 or a placebo mixture of compressed air. A double-blind, random, crossover design was used. RESULTS: Patients with panic disorder and patients with both panic disorder and obsessive-compulsive disorder showed similar strong anxiogenic reactions to 35% CO2; while patients with obsessive-compulsive disorder alone did not differ from comparison subjects. CONCLUSIONS: These results confirm that obsessive-compulsive disorder and panic disorder are two distinct syndromes and that patients with these disorders have different sensitivity to CO2 inhalation.