Background Relating a disease state to an entire population of proteins provides an opportunity to gain new insights into a disease. Methods Male populations of 53 patients with angiographic coronary artery disease and 53 control subjects without coronary disease from the Duke Databank for Cardiovascular Disease were established and matched for age and race as well as extremes of risk factors. Major plasma protein abnormalities were excluded. Plasma samples of each group were pooled to make large volumes (6 L each) to identify low-abundance proteins. After removal of albumin as well as immunoglobulins and enrichment of smaller proteins (<20-40 kDa), samples were separated into 12 960 fractions by cation exchange and 2 reversed-phase chromatography steps. Proteins were analyzed by liquid chromatography–electrospray ionization tandem mass spectrometry. Results There were 731 plasma proteins or fragments identified. Of these proteins, 95 were differentially displayed in the case versus control populations. These represent broad categories of proteins involved with natural defenses, inflammation, growth, and coagulation.