Cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory mediators. We determined the relative contribution of CPB on activation of cytokines and adhesion molecules in patients undergoing coronary revascularization by comparing them with patients receiving off-pump coronary artery bypass grafting (OPCAB). Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13), or were treated conventionally using extracorporeal circulation, blood cardioplegia, and hypothermic arrest (29 degrees C-31 degrees C; n = 13). Systemic levels of TNF-alpha and the soluble adhesion molecules P-selectin and intracellular adhesion molecule 1 (ICAM-1) were assayed. Immunohistochemistry was used to account for cardiac-specific expression of adhesion molecules in interventricular endomyocardial sections. Both systemic and endomyocardial expression of adhesion molecules were lower in the OPCAB group. Coronary revascularization with CPB resulted in a significant higher expression of TNF-alpha, which was associated with P-selectin and ICAM-1 expression. This was accompanied with higher catecholamine requirement in the CPB group in the early postoperative period. Despite comparable surgical trauma, the OPCAB procedure without the use of CPB and cardioplegic arrest significantly reduces systemic and cardiac adhesion molecule expression and catecholamine requirement. Since the clinical course in the early postoperative period was comparable, larger trials are required to select the appropriate patient who benefits most from one or the other treatment regime.