The authors have developed a method for profiling plasma lipoproteins based on differences in their surface chemical properties using HPCE. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were used as model compounds representing components of the lipoprotein population with high surface polarity (HDL) and low surface polarity (LDL). Using an uncoated fused-silica capillary in the HPCE measurement, the effective electrophoretic mobilities (mu eff) of HDL and LDL at high pH were found to be nearly identical in different buffer systems and ionic strengths. Both HDL and LDL particles have a high affinity for dodecyl sulfate anions (DS-), increasing the mu eff for both particles by almost a factor of two but not giving significantly different mu eff values. Decreasing the polarity of the solution by the addition of acetonitrile resulted in a partitioning of the DS- ions between the solvent and lipoprotein particles. The more hydrophobic LDL particles retain a larger fraction of DS- ions than do HDL particles. Under these conditions, the LDL particles have a significantly higher charge/volume ratio than do HDL particles and a large difference in mu eff values is achieved. The conditions for maximizing the mu eff difference were found by studying the influence of the concentration of the DS- ions and percent acetonitrile of the mu eff of LDL and HDL at high pH.