We investigated the relationship between cardiac output and PETCO2 as well as blood PCO2 in 10 patients undergoing cardiac surgery of long duration under high-dose fentanyl anesthesia. After anesthetic induction, the minute ventilation was kept constant at 10 ml.kg-1 x 10 cycles.min-1 and a pulmonary artery catheter was inserted. PETCO2, PaCO2 and cardiac index (CI) were measured simultaneously. PaCO2 was corrected for body temperature, and alveolar dead space-to-tidal volume ratio was calculated as VD/VTalv = (PaCO2-PETCO2)/PaCO2. After body, temperature became stabilized, the measurements were started and repeated every 10 to 20 minutes during the prebypass period. One hundred and eight sets of data were taken from 10 patients. PETCO2 correlated positively with CI. Similarly, PaCO2 correlated positively with CI, but VD/VTalv, did not correlate with CI. PETCO2 correlated closely and positively with PaCO2, but it correlated negatively and only marginally with VD/VTalv. When examined in individual patients, PaCO2 correlated positively with PETCO2 in all patients, while VD/VTalv correlated negatively with PETCO2 only in 3 patients. By multiple regression analysis, VD/VTalv change accounted for only 22.3 +/- 15.0% of PETCO2 change, while PACO2 or PaCO2 change accounted for 77.6 +/- 15.0% of PETCO2 change. Decreased CI was associated with decreased CO2 delivery from the tissue to the lung (DCO2) and PaCO2 decreased with decreasing DCO2. Decreased CI was also associated with decreased oxygen uptake (VO2), and PaCO2 decreased with decreasing VO2. A decrease in CI resulted in an increase in VA/Q, and PaCO2 decreased when VA/Q increased. PETCO2 decreased when cardiac output decreased. A decrease in PACO2 explained the decrease in PETCO2 better than an increase in VD/VT did. Decreased cardiac output might cause hypocapnia through decreased CO2 delivery to the lung, decreased CO2 production and/or increased ventilation-to-perfusion ratio.