Controversy has been raised about the effects of systemic carbon dioxide accumulation versus the intra-abdominal pressure on hemodynamics during laparoscopy. We compared the acid-base and hemodynamic changes during pneumoperitoneum in a randomized cross-over study between CO2 and nitrogen gases to test the hypothesis that the CO2 absorbed during laparoscopy, rather than the 15 mmHg intra-abdominal pressure created, accounted for these changes. Eight adult pigs were anesthetized and ventilated with a fixed minute ventilation. Metabolic function was measured from analysis of expired flow by a metabolic measurement cart. After baseline periods, animals were randomized into two groups, for 2 hr of either CO2 or nitrogen pneumoperitoneum at 15 mmHg intra-abdominal pressure, followed by 1 hr of recovery. After at least a 48-hr recovery period, the experiment was repeated with the other gas. Metabolic data revealed that there was a significant absorption of CO2 gas across the peritoneal epithelium during CO2 pneumoperitoneum. Animals insufflated with CO2 gas experienced a 75% increase in pulmonary CO2 excretion, with significant acidemia and hypercapnia, whereas there were no acid-base disturbances in those with nitrogen insufflation. Oxygen consumption remained essentially unchanged in both groups, even during pneumoperitoneum. CO2 pneumoperitoneum was also associated with systemic and pulmonary arterial hypertension and a reduction in stroke volume of up to 15%. Pneumoperitoneum alone did not compromise hemodynamics. Pneumoperitoneum using CO2 gas during laparoscopy resulted in systemic CO2 absorption across the peritoneum. This led to acidemia, hypercapnea, and depressed hemodynamics. The intra-abdominal pressure routinely used during laparoscopic surgery did not affect metabolic function, acid-base balance, or hemodynamics in the experimental model.