To investigate the possible role of atrial and brain natriuretic peptides (ANP and BNP) in the renal effects of mechanical ventilation with positive end-expiratory pressure (PEEP), we measured changes in plasma ANP and BNP levels during PEEP in patients undergoing subtotal esophagectomy. Application of 15 cm of H2O PEEP for 1 h decreased the levels of plasma ANP and BNP from 24.4 +/- 5.5 (mean +/- SEM) and 19.0 +/- 3.5 fmol/mL to 14.4 +/- 2.1 and 15.3 +/- 3.0 fmol/mL, respectively (P < 0.05). The level of plasma cyclic guanosine monophosphate, an intracellular second messenger of ANP and BNP, also decreased from 8.4 +/- 1.5 to 5.7 +/- 0.8 pmol/mL (P < 0.05). PEEP increased the levels of plasma arginine vasopressin from 2.0 +/- 0.5 to 4.2 +/- 1.2 pg/mL, aldosterone from 36.1 +/- 4.9 to 65.3 +/- 12.7 pg/mL, and plasma renin activity from 1.4 +/- 0.5 to 2.7 +/- 0.7 ng.mL-1.h-1. During PEEP ventilation, urine output, urinary sodium and potassium excretion, osmolar clearance, and cardiac index all decreased. PEEP increased free water clearance, right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure. The level of plasma endothelin, mean blood pressure, and heart rate did not change significantly. These results suggest that not only hemodynamics and the vasopressin and renin-angiotensin-aldosterone system, but also the natriuretic peptide system (ANP and BNP), are involved in the renal effects of PEEP.