Both retroperitoneoscopic and laparoscopic surgical approaches to kidney and adrenal gland have been reported but their cardiopulmonary pathophysiology has been incompletely characterized. To test the hypothesis that these approaches have markedly different impact on the circulatory and respiratory systems, we assessed at similar insufflation pressures alterations in cardiovascular and respiratory variables during retroperitoneal and intraperitoneal CO2 insufflation. Eighteen healthy, anesthetized (propofol, alfentanil, vecuronium), mechanically ventilated pigs were randomly instrumented for either retroperitoneoscopic (n = 9) or laparoscopic (n = 9) surgery. After CO2 insufflation cardiovascular and respiratory variables were measured at four cavity pressures (baseline, 10, 15, and 20 mmHg), while end-expiratory CO2 tension was maintained by adjusting tidal volume. Data were analyzed for both insufflation-pressure-dependent and group effects by one-way and two-way ANOVA for repeated measurements, respectively, followed by Newman-Keuls post hoc test (P < 0.05). Cardiac output, mean arterial, pulmonary artery, central venous, and femoral venous pressures increased significantly in both groups in an insufflation-pressure-dependent fashion. However, changes in cardiac output (P < 0.001), pulmonary artery (P < 0.007), central venous (P < 0.001), and iliac venous pressures (P < 0.001) for the same insufflation pressure were markedly and significantly greater with intraperitoneal than retroperitoneal CO2 insufflation. Most important, intraperitoneal unlike retroperitoneal insufflation induced a marked inferior vena caval pressure gradient (8.9 +/- 1.1 mmHg vs 1.0 +/- 0.5 mmHg, P < 0.00001). While both retroperitoneal and intraperitoneal CO2 insufflation required increased tidal volumes to adjust endtidal CO2 tension to baseline, intraperitoneal CO2 insufflation resulted in a significantly greater increase of mixed venous and arterial carbon dioxide tensions (P < 0.007) even at similar insufflation pressures. Furthermore, significantly greater peak airway pressures (P = 0.018) were required with intraperitoneal than with retroperitoneal insufflation to administer the same tidal volume, indicating a greater decrease in quasi-static compliance with intraperitoneal insufflation (P = 0.0436). Thus, (i) cardiovascular and respiratory changes are much less during retroperitoneal than intraperitoneal CO2 insufflation, even at the same insufflation pressures, and (ii) retroperitoneal CO2 insufflation unlike intraabdominal CO2 insufflation does not induce an inferior vena caval pressure gradient and hence does not appear to impair systemic lower body venous return up to insufflation pressures of 20 mmHg.