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OBJECTIVE: Considerable evidence suggests a connection between panic disorder and respiration, but the nature of the respiratory abnormalities in panic disorder remains unclear. The authors investigated the breath-by-breath complexity of respiration dynamics in panic disorder. METHOD: Respiratory physiology was assessed in 40 patients with panic disorder and 31 healthy comparison subjects by using a breath-by-breath stationary system for testing cardiorespiratory function. Irregularity in the breathing pattern was determined by applying the approximate entropy index, which is an indicator of the irregularity and the “disorder” of the measure. RESULTS: The patients with panic disorder showed significantly higher approximate entropy indexes than the healthy subjects for the measured respiratory parameters. Sighs contributed to the irregularity of breathing patterns but did not account for all the differences in approximate entropy between the patients with panic disorder and the comparison subjects. Anxiety state, severity of illness, and somatic and individual variables such as participation in sports and cigarette smoking did not seem to influence the results. CONCLUSIONS: Patients with panic disorder showed greater entropy in baseline respiratory patterns, indicating higher levels of irregularity and complexity in their respiratory function. Greater respiratory entropy could be a factor in vulnerability to panic attacks.