Cardiac operations with cardiopulmonary bypass cause a systemic inflammatory response, which can lead to organ injury and postoperative morbidity. Causative factors include surgical trauma, contact of blood with the extracorporeal circuit, and lung reperfusion injury on discontinuing bypass. Advances in immunological techniques have allowed measurement of both plasma and intracellular components of this multifaceted perioperative response. This includes activation of the complement, coagulation, fibrinolytic, and kallikrein cascades, activation of neutrophils with degranulation and protease enzyme release, oxygen radical production, and the synthesis of various cytokines from mononuclear cells (including tumor necrosis factor, interleukin-1, and interleukin-6). Advances in our understanding of the interactions between these markers of cellular and humoral responses to cardiopulmonary bypass will enable more effective intervention to reduce the deleterious effects and improve the outlook for patients undergoing cardiac operations beyond the 1990s.