Human pooled albumin has traditionally been used both to pacify the artificial surfaces in a cardiopulmonary bypass circuit and also for volume repletion following surgery. In evaluating the routine use of albumin in multiple phases of cardiac surgery, conscientious surgical teams must assess both the physiological and financial price of albumin. Albumin indiscriminately binds many plasma proteins and lipids. In this series of experiments, we explored the influence of highly purified albumin devoid of bound lipids and globulins on both receptor-dependent (FMLP) and receptor-independent (PMA) priming/activation of human neutrophils. We believe that it is important to distinguish the direct influence of albumin from the albumin-bound proteins and lipids. We, therefore, also examined the effect of clinically accessible human pooled albumin on human neutrophils. We observed a dose-dependent priming/activation (elastase release) of human neutrophils by both pooled and purified albumin. We conclude that it is increasingly difficult to justify the routine use of albumin in cardiac surgical patients.