The end-tidal carbon dioxide (CO2) concentration has been found to correlate with cardiac output during and after cardiopulmonary resuscitation (CPR) in animal models. We monitored end-tidal CO2 values continuously during cardiac resuscitation in 23 humans while ventilation was held constant with a computer-controlled CPR Thumper. This report focuses on ten of the 23 patients who experienced return of spontaneous circulation (ROSC) during monitoring. There was no significant difference in the end-tidal CO2 value of patients without ROSC (1.8% +/- 0.9%) and the end-tidal CO2 value of patients before ROSC in patients who had ROSC (1.7% +/- 0.6%). The end-tidal CO2 concentration increased immediately in all patients who had ROSC, from 1.7% +/- 0.6% to 4.6% +/- 1.4%, then gradually returned to a new baseline (3.1% +/- 0.9%). Change in the end-tidal CO2 value was often the first clinical indicator that ROSC had occurred. Our findings suggest that end-tidal CO2 monitoring may provide clinically useful information that can be used to guide therapy during CPR.