Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, is quantified in a number of ways, typically by immunochemical methods. Commercial tests do not discriminate among isoforms of apo A-I. Two-dimensional electrophoresis, however, segregates and differentiates these isoforms, primarily due to charge variations among the various species. Stained two-dimensional gels can be scanned using high-resolution laser densitometry, and the isoforms can then be quantified using image analysis software. Human sera from coronary heart disease (CHD) patients (n = 36) and sex-matched and close-age-matched individuals (n = 36) with no known CHD were analyzed, to determine the relative abundance for each isoform within a given serum. In this preliminary study, we observed statistically significant differences between the two groups, suggesting altered post-translational processing from the proapo A-I and mature apo A-I isoforms to their adjacent isoforms for patients with histories of heart disease. In two instances, the P values were less than 0.005; in two others, P values were less than 0.001.