OBJECTIVES: To determine the effect of cardiopulmonary bypass (CPB) on renal medullary oxygenation. DESIGN: Observational. SETTING: Laboratory. PARTICIPANTS: Pigs (n=3). INTERVENTIONS: Following induction of general anesthesia, a Paratrend blood gas probe was placed directly into the left renal medulla. Two animals were subjected to 90 min of CPB, while a third served as a non-CPB control. A probe was also placed in the left renal pelvis of one (CPB) animal to allow direct urine PO2 measurements. MEASUREMENTS AND MAIN RESULTS: Medullary hypoxia (PO2 <65 mmHg) was evident prior to CPB. With the onset of CPB, medullary PO2 further declined to nearly unmeasurable levels; PCO2 and pH were unchanged. Brief circulatory arrest during CPB in one animal resulted in rapid additional PCO2 rise and pH decline that corrected with reperfusion. Following the cessation of CPB, medullary PO2 gradually increased, but remained lower than pre-CPB levels. No changes in medullary PO2 were observed in the sham animal. Renal pelvis urine PO2, but not pH or PCO2, appeared to correlate with medullary values at all times. CONCLUSIONS: Our findings indicate that renal medullary hypoxia is extreme during CPB and may persist following CPB. These data suggest a basis for the vulnerability of the kidney to injury during cardiac surgery. Renal pelvis urine PO2 appears to correlate closely with medullary PO2 and may be a useful tool for studying medullary oxygenation during CPB in humans.