The accuracy and advantages of determining percentage of hemoglobin oxygen saturation of whole blood by advanced instruments of oximetry, gas chromatography, and the computation of oxygen saturation from pO2 and pH data are compared with the Van Slyke-Neill manometric method. It was found that oximetry is extremely fast, less expensive, and more accurate than in the past, the apparatus requires little training to operate and has diminutive service maintenance. The gas chromatograph proved to be highly accurate and could serve as a standard calibration check method in place of the more time-consuming Van Slyke-Neill apparatus for oximetry and pO2 and pH electrode instrumentation. Computation of O2 saturation from pO2 and pH data also proved to be accurate, confirming that this method is more useful during cardiac surgery because it can provide additional acid-base information. In the low oxygen saturation range (less than 60%), all three methods proved to be of similar sensitivity.