Experimental filtration mitigates the accumulation of PMN priming activity and lipid priming activity in the supernatant of RBC units during routine storage. Priming of the fMLF-activated, superoxide dismutase inhibitable respiratory burst (nmol O2−/min) is depicted as a function of experimental filtration groups and days of routine storage (A). The standard leukoreduced controls (standard LR filter) demonstrate the accumulation of PMN priming activity as a function of storage with significant activity reached by day 21 with a relative maximum on day 42 of storage (*P < .05 vs day 1 supernatant). In the 3 experimental filters (B, P, and M), there is only an increase in priming activity in the RBC supernatants on day 42 vs day 1 (*P < .05 vs day 1 supernatant). The priming activity from supernatants from RBC units that underwent standard LR was significant from the experimental filtration groups on both day 21 and day 42 (†P < .05 vs day 21 and day 42 supernatants from experimentally filtered RBC units; n ≥ 10 for each group). Experimental filtration inhibited the accumulation of lipid priming activity in the supernatant of RBC units during storage (B) depicted as the maximal rate of superoxide anion production to fMLF (nmol O2−/min) as a function of treatment group. The lipid extracts from the supernatant of the RBCs that underwent standard LR or experimental filtration were not different from albumin-treated controls. However, extracts from the supernatant of RBCs that underwent standard LR demonstrated increased priming activity as compared with albumin-treated controls and extracts from day 0 and day 42 supernatants from experimentally filtered RBCs (*P < .05 vs albumin controls and lipid extracts from day 1 supernatants, †P < .05 vs day 42 extracts or the supernatants of experimentally filtered RBCs; n = 15). Lastly, the extracts from the supernatants of experimentally filtered RBC units showed greater priming activity vs the albumin-treated controls and the extracts from the day 0 experimentally filtered extracts (*P < .05 vs albumin controls and lipid extracts from day 1 supernatants).