Decellularization treatment of heart valves has been thought to eliminate tissue immunogenicity. Early failure of tissue-engineered xenogeneic heart valves was seen in children and has been a major drawback in this promising field of research. This study was designed to characterize the effects of acellular porcine heart valve tissue on immune activation in vitro. Incubation of decellularized porcine tissue with human plasma led to adsorption of IgG, activation of the classical complement pathway and adhesion of activated polymorphonuclear leukocytes (PMN). This inflammatory response was strongly inhibited by proteins extracted from native porcine tissue which might indicate that inhibitors of PMN activation present in the extracellular matrix (ECM) are lost during the decellularization process.