To determine the accuracy of four pulse oximeters during mild and moderate arterial hypoxemia, we produced stepwise arterial blood desaturation in 25 healthy, nonsmoking volunteers by adjusting the inhaled oxygen concentration. At plateaus of < 80%, 85% to 90%, 90% to 95%, and 95% to 100%, pulse oximetry saturation (SpO2) was measured with the four different monitors: Dinamap Plus Model 8700, Oxyshuttle, Ohmeda 3700, and MiniOx IV. Arterial blood samples were analyzed with a co-oximeter and the arterial oxyhemoglobin saturation (SaO2) was compared with the SpO2 readings at each plateau. Significant deterioration in the accuracy of pulse oximeters was observed as SaO2 decreased. In 14 instances of hypoxemia (SaO2 < 90%), subjects exhibited SpO2 values greater than 90%. In conclusion, the accuracy of pulse oximetry deteriorates as hypoxemia worsens. Confirmation of arterial blood oxyhemoglobin saturation by co-oximetry is necessary when precise determination of arterial oxyhemoglobin level is critical.