HDL apolipoproteins (apo) from normal subjects and patients with multiple myeloma were studied by isoelectric focusing (IEF) and by two-dimensional gel electrophoresis. Qualitative abnormalities were detected in myeloma HDL apolipoproteins. We observed two new bands not previously described in this disease. As determined by IEF and two-dimensional gel electrophoresis, the relative molecular weight of these two proteins was 12,600, with pI = 6.04 and 6.36, respectively. They correspond to two isoforms of serum amyloid A protein (SAA), as confirmed by western blot assay against specific antiserum to SAA. The high sensitivity of this assay revealed also other SAA isoforms. Our data are consistent with the hypothesis that major apolipoproteins of normal HDL, apo A-I and apo A-II, could be displaced by SAA isoproteins in myeloma HDL. This could lead structural changes in HDL.