Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express Fc gamma RIIIa (CD16) identical to that in NK cells, but with a cell type-specific glycosylation. The Fc gamma RIIIa molecules are released from the cell surface on activation, and these soluble forms (sFc gamma RIIIa) are present in plasma. We measured sFc gamma RIIIaM phi in plasma by Immuno-PCR with newly-developed anti-Fc gamma RIII mAb, MKGR14 (mIgM), which recognizes Fc gamma RIIIaM phi specifically. In healthy donors, the level of sFc gamma RIIIaM phi increased with age, and was positively correlated with LDL-cholesterol to HDL-cholesterol ratios and LDL-cholesterol, but negatively with HDL-cholesterol. In addition, the sFc gamma RIIIaM phi level was related to the number of risk factors for atherosclerosis and correlated with carotid maximum intima-media thickness in subjects for annual medical checkup. The sFc gamma RIIIaM phi level was significantly increased in patients with coronary artery disease (CAD) with atherosclerosis, but not in patients with vasospastic angina (VSA) or intact coronary artery, compared with age-matched healthy donors. The sFc gamma RIIIaM phi level was related to the number of significant coronary artery stenoses, and positively correlated with LDL-cholesterol to HDL-cholesterol ratios and lipoprotein (a), but negatively with HDL-cholesterol. These findings suggest that the macrophages are activated during the incipient stage of atherosclerosis, and that sFc gamma RIIIaM phi may serve as predictive marker for atherosclerosis.