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As part of a study on the mechanisms of leukocyte filtration, the influence of pore size distribution on filter efficiency was investigated. Conventional leukocyte filters are not suitable for model studies, as these filters are composed of tightly packed synthetic fibers, with a poorly defined porous structure. Therefore, open cellular polyurethane membranes with pore size distributions varying from approximately 15 to 65 microns were prepared. Filtration experiments with stacked packages of these membranes showed that leukocytes are best removed (greater than 99%) by filters with a pore size distribution of 11-19 microns. These pore sizes approach the size of leukocytes (6-12 microns). However, due to fast clogging, blood flow through these filters is rapidly reduced, which results in a low filter capacity. With an asymmetric membrane filter, in which the pore size decreases from about 65 to 15 microns in the direction of blood flow, both moderate removal of leukocytes (greater than 80%) and maintenance of flow (approximately 0.2 mL/s) are obtained. This results in efficient leukocyte removal. From cell analysis of both filtrate and filter, it is concluded that adhesion rather than sieving is the major filtration mechanism. Thus, further optimization of the filter may be achieved by surface modification.