OBJECTIVE To assess pulmonary hemodynamics and alveolar oxygenation in dogs anesthetized with propofol or isoflurane during one-lung ventilation (OLV) in a closed-thoracic experimental model. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized with each of 3 protocols (constant rate IV infusion of propofol [0.4 to 1.0 mg/kg/min], isoflurane at the minimum alveolar concentration [MAC], and isoflurane 1.5 MAC), with a 7-day washout period between anesthetic sessions. During each session, dogs were intubated with a double-lumen endotracheal tube, positioned in right lateral recumbency, and administered atracurium (0.1 to 0.2 mg/kg, IV, q 30 min) to allow mechanical ventilation throughout a 2-hour observation period. Dogs underwent two-lung ventilation for 30 minutes, OLV of the right lung for 1 hour, and two-lung ventilation for another 30 minutes. Pulmonary hemodynamic and blood gas variables were evaluated at predetermined times and compared among protocols and over time within each protocol. RESULTS Alveolar oxygenation was not impaired, and mean heart rate and pulmonary artery pressure and occlusion pressure were similar among the 3 protocols. One-lung ventilation caused a significant increase in the arteriovenous shunt fraction only when dogs were anesthetized with isoflurane at 1.5 MAC. Dogs developed respiratory acidosis, which was exacerbated by OLV, during all anesthetic sessions. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated pulmonary hemodynamics and alveolar oxygenation during OLV in a closed-thoracic model were similar regardless of whether dogs were anesthetized with propofol or isoflurane. One-lung ventilation can be successfully performed in dogs by use of a double-lumen endotracheal tube and either propofol or isoflurane.