Background-The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-␣, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques. Methods and Results-Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-␣ receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (PϽ0.05). TNF-␣ receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach. Conclusions-There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma.