Surveys of national and international laboratories indicate that among-laboratory and between-laboratory sources of variance account for the majority of variability in laboratories measuring apolipoproteins A-I and B. These sources of variance are amenable to correction through the use of common quality control and reference materials. We utilized proven techniques employing ethyl alcohol and acetate buffer to precipitate either apolipoprotein A-I rich or apolipoprotein B rich fractions that were blended with whole or delipidated serum producing five pilot-sized pools containing graded levels of apolipoproteins. After lyophilization the pools were tested and each pool contained levels of analytes similar to frozen serum and contained varied amounts of apolipoproteins A-I and B. Temporal and accelerated thermal stability testing demonstrated stability of the analytes in the pools with time (three years) and temperature (up to 56 degrees C). This technology provides a preparative procedure for apolipoprotein reference materials over the extended range needed in clinical applications.