BACKGROUND: The wall lift method (W), which was introduced to reduce the adverse effects of CO2 pneumoperitoneum (P), induces an excessive stress response and may be imposed for significant adverse reactions. This study was undertaken to compare the physiologic response of the CO2 pneumoperitoneum and wall lift methods. METHODS: Thirty-two patients were randomly divided into two groups (the P and W). Gastric intramucosal PrCO2, CO2 gap, intramucosal pH (pHi), and plasma concentration of epinephrine and norepinephrine were measured: after the induction of anesthesia, during operation, at the end of the operation, and after operation. Serum concentrations of TNF-alpha and IL-6 were measured at 24 hours before operation, and 24 hours, and 72 hours after operation. The TNF-alpha and IL-6 levels of peritoneal macrophages were also measured. Urine output was measured during operation. RESULTS: PrCO2 and CO2 gap increased during and after the operation in P, and after the operation in W, and pHi decreased during and after operation in P, and after operation in W. Urine output was higher in W. Epinephrine and norepinephrine increased in both groups, but epinephrine was higher in W at the end of the operation. TNF-alpha and IL-6 increased postoperatively and the magnitude of these increases were similar in both groups. The level of TNF-alpha and of IL-6 in peritoneal macrophage were similar in both groups. CONCLUSIONS: We conclude that; CO2 pneumoperitoneum induces intestinal mucosal acidosis, the wall lift method induces more significant stress response, and the magnitude of immune response is similar for both methods.