To obtain information in vivo concerning the role of Fcgamma receptors (FcgammaR) in atherosclerosis, we used quantitative flow cytometry to measure the levels of expression of FcgammaRI and FcgammaRIIA on peripheral monocytes in patients with severe atherosclerosis. Expression of several other markers was also measured. We found that differences in the levels of expression of FcgammaRI were not statistically significant when compared between patients and control subjects. For FcgammaRIIA, levels of expression were decreased in the patient group, a difference that was statistically significant. Levels of expression of CD14 and CD36 were also significantly decreased in the patient group. The decrease in expression of FcgammaRIIA was statistically significant when the effects of current cigarette smoking status or medication use, including statins, were taken into account. There was also a positive and statistically significant correlation between high-density lipoprotein-cholesterol and levels of expression of FcgammaRIIA for all subjects. In contrast, decreased levels of expression of CD14 and CD36 were strongly associated with current smoking status or statin use. In summary, levels of expression of FcgammaRIIA on peripheral blood monocytes were significantly decreased in patients with clinical atherosclerosis. Additional studies are warranted to determine if levels of expression of FcgammaRIIA have utility as a phenotypic marker for assessing relative risk of atherosclerotic disease.