BACKGROUND: Monitoring of cellular function during acute reduction of oxygen delivery(DO2) remains controversial. Increases of arteriovenous difference in PCO2(AVPCO2) and in pH(AVpH) have been alleged to reflect development of tissue hypoxia in shock status associated with low cardiac output. Method: 6 anesthetized and mechanically ventilated pigs were bled via Swan-Ganz catheter by 10% of total estimated blood volume. In each pig, we measured the hemodynamic parameters, arterial and mixed venous blood gas analysis data and calculated O2-derived parameters during gradual blood loss from 10% to 50%. RESULT: As blood loss increased, DO2 declined from 521+/- 108 ml/min to 178+/- 125 ml/min but O2 extraction ratio(14+/- 4% to 47+/- 33%) increased. After 30% blood loss, O2 consumption decreased from 121 +/-48 ml/min to 79+/- 58 ml/min progressively but lactate level markedly increased from 22.0 +/-5.5 mg/dl to 52.7+/- 21.8 mg/dl. As DO2 decreased, AVPCO2 and AVpH( -11+/- 2 mmHg to - 27+/- 11 mmHg, 0.03+/- 0.02 to 0.11 0.04 respectively) rose, and these increases were especially more prominent after DO2 value at 30% blood loss than before(p<0.05). CONCLUSION: We demonstrated that the increases of AVPCO2 and AVpH can be reliable parameters of tissue hypoxia during gradual blood loss.