In studies of the plasma proteome, the high abundance of proteins such as albumin and immunoglobulin impedes the investigation of lower abundance proteins that may be more suitable as biomarkers of disease. We report the specific removal of 98% of albumin and 80% of immunoglobulin heavy chain from human plasma by affinity chromatography, and the subsequent improvement in the number of spots detected and their resolution following two-dimensional gel electrophoresis.