Atherosclerosis is the underlying disease process in patients affected with coronary artery diseases (CAD). Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express Fcgamma receptor type IIIa (FcgammaRIIIa: CD16) identical to that in natural killer cells (NK cells), but with a cell type-specific glycosylation. In contrast, neutrophils express FcgammaRIIIb. These FcgammaRIIIs are released from the cell surface on activation, and these soluble forms (sFcgammaRIII) are present in the plasma. We measured sFcgammaRIIIa(Mphi) in the plasma with a newly developed anti-FcgammaRIII mAb, MKGR14, which recognizes FcgammaRIIIa(Mphi) specifically. The level of sFcgammaRIIIa(Mphi), as well as the level of sFcgammaRIIIa (sFcgammaRIIIa(Mphi) plus sFcgammaRIIIa(NK)) or the level of total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb), were significantly increased in patients with CAD, but not in patients with vasospastic angina (VSA) or intact coronary arteries, compared with age-matched healthy donors. The sFcgammaRIIIa(Mphi) level was related to the number of significantly affected coronary arteries, and positively correlated with LDL-cholesterol to HDL-cholesterol ratios, but negatively with HDL-cholesterol. No correlation among the levels of three sFcgammaRIIIs was observed in CAD patients, as well as in healthy donors. The macrophages are activated during the process of atherosclerosis, and sFcgammaRIIIa(Mphi) may serve as a novel marker for atherosclerosis.