Strategies for diminishing the risk of blood transfusion-associated transmission of HIV-1 were evaluated. HIV-1-infected peripheral blood mononuclear cells were added to blood that was subsequently filtered by using different white cell (WBC) filters (cellulose acetate and polyester). The average log reduction of infected cells with polyester filters was at least 2.5 as measured by ID50 titration and polymerase chain reaction. In two WBC filtration experiments with blood from seropositive donors diluted 1:4 with seronegative blood, log reductions of 2.4 and greater than 2.5 were observed. No cell-free virus was retained by the filter used. A freeze-thaw procedure applied to HIV-1-contaminated blood resulted in a minimal log reduction. These results indicate that the reduction of HIV-1 infectivity as a result of filtration is mainly due to the removal of HIV-1-infected WBCs, and that complete removal of infected WBCs cannot be achieved by the current filtration or freeze-thaw procedures. However, the development of filters with enhanced ability to remove (possibly infected) WBCs may have the added benefit of improving the safety of donor blood, especially in multiply transfused patients.