Background-Given growing evidence that respiratory dysregulation is a central feature of panic disorder (PD) interventions for panic that specifically target respiratory functions could prove clinically useful and scientifically informative. We tested the effectiveness of a new, brief, capnometry-assisted breathing therapy (BRT) on clinical and respiratory measures in PD.Methods-Thirty-seven participants with PD with or without agoraphobia were randomly assigned to BRT or to a delayed-treatment control group. Clinical status, respiration rate, and end-tidal pCO 2 were assessed at baseline, posttreatment, 2-month and 12-month follow-up. Respiratory measures were also assessed during homework exercises using a portable capnometer as a feedback device.Results-Significant improvements (in PD severity, agoraphobic avoidance, anxiety sensitivity, disability, and respiratory measures) were seen in treated but not untreated patients, with moderate to large effect sizes. Improvements were maintained at follow-up. Treatment compliance was high for session attendance and homework exercises; dropouts were few.Conclusions-The data provide preliminary evidence that raising end-tidal pCO 2 by means of capnometry feedback is therapeutically beneficial for panic patients. Replication and extension will be needed to verify this new treatment's efficacy and determine its mechanisms.