The primary goal of this study was to evaluate differences in carbon dioxide metabolism between patients undergoing transperitoneal or extraperitoneal laparoscopic pelvic lymph node dissection (L-PLND) for staging of adenocarcinoma of the prostate (CaP). Eighteen candidates undergoing L-PLND were divided between the transperitoneal (N = 12) and extraperitoneal (N = 6) approaches. End-tidal partial pressure of CO2 (PeCO2) and minute volume of expired CO2 (VCO2) were considered indicators of CO2 absorption. These two parameters were monitored intraoperatively utilizing a metabolic cart and Ohmeda Rascal-II. The cardiostimulatory effect of increasing serum CO2 and the ventilatory countermeasures used to correct the iatrogenic hypercapnia associated with CO2 insufflation were also measured. With the exception of the region of CO2 insufflation, the operative procedure and perioperative care were identical for the two groups. Preoperative patient characteristics were similar. The mean time of CO2 insufflation was 136 minutes for the transperitoneal group and 120 minutes for the extraperitoneal group. The absorption of CO2 was significantly greater and more rapid during extraperitoneal L-PLND. This may be attributable to more profound CO2 absorption from the parietal peritoneal surface compounded by subcutaneous CO2 emphysema. Disruption of microvascular and lymphatic channels during the development of the extraperitoneal working space facilitates direct CO2 absorption into the intravascular space. A minor increase in heart rate and systolic blood pressure was noted during CO2 insufflation. In all but one patient (extraperitoneal group), hypercarbia and acidemia were prevented by an increased ventilatory rate. The potential dysrhythmogenicity of hypercarbia may contraindicate the extraperitoneal approach in patients with cardiopulmonary disease.