The goals of this study were toa) confirm prior evidence that the respiratory stimulant doxapram induces panic attacks and produces excessive hyperventilation in patients with panic disorder and b) explore the impact of cognitive mediators on symptom and respiratory responses. Method: Thirty-two subjects (16 patients and 16 controls) received doxapram (0.5 mg/kg) and placebo infusions while symptom, respiratory, and heart rate responses were monitored. Subjects were randomly assigned to receive either a standard introduction or a cognitive intervention designed to reduce the panic responses of panic patients to laboratory challenges. Results: Doxapram was a potent and specific panicogenic agent, inducing panic in 75% of patients and 12.5% of controls. Compared with controls, patients also showed a greater decrease in end tidal carbon dioxide (CO2) and greater increases in minute ventilation, respiratory frequency, and heart rate. The cognitive intervention substantially attenuated the excessive hyperventilatory response of patients but did not fully normalize their breathing patterns. Tidal volume was the only respiratory measure not significantly altered by the cognitive intervention. Conclusions: In patients with panic disorder, doxagram (0.5 mg/kg) triggers panic attacks about as potently as 7% CO2and more potently than 5% CO2or lactate. Psychological factors can modulate the appearance of ventilatory abnormalities in panic patients, but persistent respiratory disturbances were still seen. Psychological factors and respiratory physiology both appear to be important phenomena in laboratory panic.