A common accuracy-based standardization program is indispensable for establishing reference intervals for the clinical use of apolipoproteins. The development and distribution of reference materials and quality-control materials that do not exhibit matrix effects between methods is essential to the standardization process. We examined the suitability of lyophilized material as a common reference material for the measurement of apolipoproteins A-I and B. We determined values for apolipoproteins A-I and B in frozen and lyophilized serum pools, using different immunochemical approaches. We found little or no differences in apolipoprotein A-I values between frozen and lyophilized pools as determined by the different methods. In contrast, values for apolipoprotein B in lyophilized samples were consistently lower than those obtained for frozen samples. After adjusting for the effect of dilution due to reconstitution, the difference in the apolipoprotein B values for lyophilized as compared with frozen samples ranged from -26% to 4%, depending upon the assay method. Evidently, serum pools in lyophilized from are not a suitable matrix for reference materials for apolipoprotein B measurements but can be used for apolipoprotein A-I measurements.