BACKGROUND The effects of carbon dioxide pneumoperitoneum on venous return and cardiac hemodynamics during laparoscopic surgery were studied. METHODS Twelve adult pigs underwent placement of an electromagnetic flow meter across the infrarenal vena cava (IVC) as well as placement of Swan Ganz and arterial monitoring catheters. Measurements of the flow through infrarenal IVC, cardiac output (CO), pulmonary capillary wedge pressure (PCWP), mean arterial pressure (MAP), and heart rate were recorded at baseline, 5 and 60 min following insufflation to 15 mmHg with CO2, and 5 min following desufflation. Stroke volumes and systemic vascular resistance (SVR) were calculated as well. RESULTS Flow through the IVC dropped by 24 and 31% at 5 and 60 min (p = 0.03 and 0.02, respectively). Paradoxically, cardiac output rose by 14 and 28% at 5 and 60 min (p = 0.03 at 60 min). Central venous and pulmonary capillary wedge pressures rose transiently by 35 and 36% at 5 min before returning to baseline (p < 0.01). Mean arterial pressure and heart rate remained relatively constant during insufflation. Systemic vascular resistance diminished from 938 dynes/cm/s prior to insufflation to its nadir at 60 min of 650 dynes/cm/s (p < 0.01). CONCLUSIONS These observations suggest potentially complex interactions between the mechanical and systemic effects of the CO2 pneumoperitoneum on venous return. Transient elevations in cardiac filling pressures occur by an unknown mechanism, and a generalized enhanced inotropic state mediated via increased sympathetic outflow is observed in this hypercapnic anesthetized animal model.