The purpose of this experimental study was to compare two methods of pulmonary blood flow manipulation during one‐lung ventilation (OLV), either reducing pulmonary blood flow to the non‐ventilated lung by inflation of a pulmonary artery catheter balloon (PAB) or by infusion of prostaglandin F2α(PGF2α). Seven anaesthetized dogs were intubated with a Kottmeier endobronchial tube and ventilated with 66% O2. Systemic and pulmonary pressures and blood gases, cardiac output and airway pressure were measured, and the venous admixture (Qsp/Q) was calculated. During two‐lung ventilation (TLV) Pao2was 43.6 1.9 kPa (mean s. d.) and (Qsp/Q) was 11 3%. OLV reduced Pao2to 12.1 1.6 kPa (P0.001) and increased Qsp/Q to 40 4% (P0.001). Mean pulmonary artery pressure and airway pressure increased. PAB inflation caused an increase in Paosb>2to 19.9 2.9 kPa (P0.02) and a decrease in Qsp/Q to 27 6% (P0.001). PGF2αinfusion (1.2 μg kg‐1min‐1) into the pulmonary artery of the non‐ventilated lung increased Pao2to 22.4 3.3 kPa (P0.001) and decreased Qsp/Q to 254 (P0.001). PGF2αinfusion resulted in a small increase in mean systemic and pulmonary artery pressures. During the infusion of 1.2 μg kg‐1min‐1of PGF2αno signs of bronchoconstriction were observed. PAB inflation and PGF2αinfusion were equally effective in improving oxygenation and reducing venous admixture during OLV. PGF2αinfusion is proposed as a practical and safe alternative to PAB inflation when application of PEEP or oxygen to the non‐ventilated lung during OLV is