The effect of double filtration plasmapheresis (DFPP) on the removal of immunosuppressive substances present in the sera of patients with advanced cancers was examined. The inhibition assay of normal lymphocyte blastogenesis to phytohemagglutinin (PHA) revealed that the serum containing immunosuppressive substances could be separated from patient blood by the first filter and the substances could be concentrated in the residual fluid by the second filter in DFPP. To selectively remove the substances and to elevate the recovery of protein, a 3A-10 second filter was selected according to the elimination index. DFPP using 3A-10 was performed in 22 patients with advanced cancers. The suppressive effects of patient sera on PHA blastogenesis and on a mixed lymphocyte reaction between normal and patient lymphocytes were remarkably reduced after DFPP. Immunosuppressive substances with larger molecular weights than globulin were effectively removed by DFPP. The PPD skin-test as an index of cellular immunity in vivo improved in 62% (8/13), and performance states according to the Karnofsky's classification showed improvement in 50% (11/22) of the patients. These results suggest that the immune activity of cancer patients can recover after removal of immunosuppressive substances by means of DFPP without using a large amount of substitutional fluid.