Background and objectives: Prestorage leukoreduction offers a variety of potential benefits and is becoming more commonly practiced. The LeukoNet prestorage leukoreduction filtration system is intended for leukoreduction of red blood cells and uses a vent to allow automatic drainage of red cells from the filter. Materials and methods: We studied the functional characteristics and the invivo and in-vitro properties of leukoreduced AS-1 Red Blood Cells prepared with this new system. Units of AS-1 Red Blood Cells were filtered at 4°C through the LeukoNet™ filter 24-48 h after collection and stored under usual conditions for 42 days. Residual leukocytes were enumerated using a Nageotte chamber or with a polymerase chain reaction (PCR) technique. In the clinical trial (phase one), 21 donors had units stored with and without leukoreduction for 42 days; biochemical assays were done before and after storage, and 51Cr/99mTc red cell recovery studies at the end of the storage period. Results: Leukocyte content after filtration was 3.2±2.6×10^4/unit (n = 21), and all units had