Aims: It is still unknown whether elevated C-reactive protein levels are responsible for coronary microcirculatory dysfunctionin patients with coronary artery disease(CAD). This study was aimed at evaluating the association between C-reactive protein levels and endothelium-dependent and endothelium-independent coronary blood flow(CBF) responses in non-culprit arteries of patients with CAD. Methods and results: We studied 28 patients(14 with normal and 14 with elevated C-reactive protein levels, > 5 mg/L) with single-vessel disease and otherwise angiographically normal coronary arteries undergoing percutaneous transluminal coronary angioplasty(PTCA). CBF was measured in the non-PTCA vessel using an intracoronary Doppler guide wire and quantitative coronary angiography at baseline, after intracoronary infusion of substance P and of adenosine, and expressed as per cent change from baseline. The increases in CBF during infusion of substance P and of adenosine were lesser in patients with elevated than in those with normal C-reactive protein levels(34± 22 vs. 61± 34% , P=0.04 and 131± 53 vs. 189± 89% , P=0.03, respectively). Multivariable analysis identified elevated C-reactive protein level as the only independent predictor of reduced response to substance P(P=0.01) and adenosine(P=0.02). Conclusion: In patients with CAD, evidence of systemic inflammation is independently associated with endothelium-dependent and endothelium-independent coronary microvascular dysfunction, which, in turn, may be critical to precipitate myocardial ischaemia, in particular, in unstable patients. Aims: It is still unknown whether elevated C-reactive protein levels are responsible for coronary microcirculatory dysfunction in patients with coronary artery disease (CAD). This study was originally at evaluating the association between C-reactive protein levels and endothelium-dependent and endothelium-independent Methods and results: We studied 28 patients (14 with normal and 14 with elevated C-reactive protein levels,> 5 mg / L) with single-vessel disease and otherwise angiographically normal coronary arteries undergoing percutaneous transluminal coronary angioplasty (PTCA). CBF was measured in the non-PTCA vessel using an intracoronary Doppler guide wire and quantitative coronary angiography at baseline, after intracoronary infusion of substance P and of adenosine, and expressed as The increase in CBF during infusion of substance P and of adenosine were lesser in patients with e levated than those with normal C-reactive protein levels (34 ± 22 vs. 61 ± 34%, P = 0.04 and 131 ± 53 vs. 189 ± 89%, P = 0.03, respectively) Protein levels as the only independent predictor of reduced response to substance P (P = 0.01) and adenosine (P = 0.02). Conclusion: In patients with CAD, evidence of systemic inflammation are independently associated with endothelium-dependent and endothelium-independent coronary microvascular dysfunction, which, in turn, may be critical to decisional myocardial ischaemia, in particular, in unstable patients.