BACKGROUND The effect of prestorage white cell (WBC) filtration on the cytokine content in red cells (RBCs) has not been clarified. METHODS Six units of buffy coat-poor RBC concentrates were prepared. Each unit was divided into three parts: one was used as a control, the second was made WBC-rich by the addition of WBCs from the buffy coat, and the third was made WBC-poor by filtration. All units were stored at 4 degrees C for 6 weeks. Immediately after preparation and every second week subsequently, samples for analyses of interleukin (IL) 1 beta (IL-1), IL-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) were obtained. After 13 weeks, the procedure was repeated on the same donors. RESULTS IL-2 was not detected. The amounts of IL-1, IL-8, and TNF alpha increased during the storage period. With the exception of IL-8, only low concentrations were found. Filtered units had lower concentrations of IL-1, IL-6, IL-8, and TNF alpha after 2 weeks of storage than did the control and WBC-rich units. The amounts of cytokines in filtered units did not increase during the study period. CONCLUSIONS Prestorage filtration seems to diminish the amount of IL-1, IL-6, IL-8, and TNF alpha RBCs during storage. The possible clinical implications of this should be elucidated.