For patients suffering from familial hypercholesterolemia, LDL-cholesterol removal may be achieved by cascade filtration in an extracorporeal process. LDH, irreversible trapping into the secondary membrane, due to mechanical or physicochemical capture, is known to be one of the main phenomena responsible for membrane fouling. This study especially focuses on the quantification and the location of LDL irreversibly trapped along the membrane by adsorption and other phenomena. The influence of filtration flux and membrane structure are studied. After an extensive washing following the plasma fractionation procedure, a gamma camera registered the In-111-labeled LDL marker tightly retained on the membrane. The same technique employing labeled magroaggregates of albumin permitted the determination of local filtration fluxes and then the calculation of local wall shear rates. LDL irreversible trapping is responsible for about 10% of the retention of LDL into the membrane. It appears to increase with increasing filtrate flow rate at constant inlet plasma flow rate. This phenomenon is enhanced near the filter outlet where the wall shear rate is minimum. No pore narrowing was observed using mercury porosimetry. The analysis of data together with membrane structure and local fluxes (tangential and transversal) leads us to postulate that a significant part of irreversible fouling occurs at the membrane surface and that the remaining internal irreversible fouling takes place in the membrane macroporous layer.