BACKGROUND: During one-lung ventilation (OLV) for thoracic surgery, hypoxic pulmonary vasoconstriction (HPV) may reduce venous admixture and ameliorate the decrease in arterial oxygenation by diverting blood from the non-ventilated to the ventilated lung. Volatile anesthethics are the drugs of choice in thoracic surgery despite numerous experimental data showing their inhibiting effect on the HPV. The object of the present study was to compare the effects of propofol with those of isoflurane on oxygenation and shunt during two lung ventilation (TLV) and OLV in human volunteers. METHODS: Thirty patients who needed OLV for an elective thoracic surgery were randomly assigned to receive either isoflurane (1 MAC isoflurane + fentanyl + vecuronium, n = 15) or propofol (2 - 3ng/ dl propofol + fentanyl + vecuronium, n = 15) with 100% oxygen in separate groups. Systemic hemodynamic data was recorded, and blood gas values were obtained 30 min after the start of TLV (TLV-30) and 30, 45 and 60 min after the start of OLV (OLV-30, 45, 60) in the lateral position. RESULTS: A significant reduction in PaO2 and increase in shunt fractions at all study times after the start of OLV compared with TLV were observed in both groups at OLV-30, 45 and 60. Percent changes of PaO2 and shunt of OLV-60 to those of TLV-30 were less in the propofol group than the isoflurane group. Other blood gas data (SaO2, SO2, PaCO2, PCO2, pH, Hb, CaO2 and CO2) and systemic hemodynamics (mean arterial blood pressure, heart rate and central venous pressure) were not different after the start of OLV compared with TLV in either group. CONCLUSIONS: TIVA with propofol was superior than isoflurane anesthesia in terms of arterial blood oxygenation and pulmonary shunting during OLV for lung surgery.