The objectives of this study were to compare continuous subjective and physiological responses of panic disorder patients and normal controls during 5% CO2 inhalation. Psychophysiological responses of panic disorder patients (n = 42) and controls (n = 25) were monitored during baseline (20 min), 5% CO2 inhalation (20 min), and recovery (20 min). The data were compared at baseline and over periods of the experiment using analysis of variance. A subgroup of patients who experienced panic attacks during the CO2 inhalation (n = 12) were significantly different from the other subjects on baseline heart rate and on variability of systolic and diastolic blood pressure, skin conductance, and breathing variability (length and number of breathing pauses and length of breathing cycle variability). Inspection of the data showed that elevation in blood pressure and breathholding were present during some of the panic attacks, suggesting that some attacks may represent a complex psychophysiological response with elements of a "freezing" reaction, well described in animal experiments, which can quickly shift to a "fight/flight" reaction that is usually characterized by an increase in heart and breathing rate. However, some patients had only minimal changes in breathing and others had minimal psychophysiological changes during the time they indicated that they had a panic attack. Panic attacks are not homogeneous and may be characterized by a variety of physiological and cognitive responses. This may indicate that biological mechanisms of panic include abnormality in many functionally connected areas of the brain responsible for complex psychophysiological reactions to multiple threatening situations.