OBJECTIVE To demonstrate that exposure to chronic inflammation results in coronary microvascular dysfunction (CMD). RESULTS Using positron emission tomography, resting and hyperaemic (adenosine, 140 microg/kg/min) myocardial blood flow (MBF) was measured in 25 patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Coronary flow reserve (CFR) was calculated as adenosine/resting MBF. Patients had normal or minimally diseased (i.e. <or=20% luminal diameter) coronary arteries at angiography and no cardiovascular risk factors. Twenty five age- and gender-matched healthy volunteers served as controls. Resting MBF was similar in patients and controls (1.25 +/- 0.27 vs. 1.15 +/- 0.24 mL/min/g; P = 0.15) while patients had lower hyperaemic MBF (2.94 +/- 0.83 vs. 4.11 +/- 0.84 mL/min/g; P < 0.001) and CFR (2.44 +/- 0.78 vs. 3.81 +/- 1.07; P < 0.001). CFR was inversely related to disease duration (r = -0.65; P < 0.001) and SLE disease activity (r = -0.69; P = 0.01). Seven patients showed ischaemic electrocardiographic changes during adenosine. They had longer disease duration (21 +/- 7 vs. 14 +/- 5 years; P = 0.03) and lower CFR (1.76 +/- 0.81 vs. 2.49 +/- 0.54; P = 0.006) when compared with patients without changes. CONCLUSIONS A reduced CFR in the absence of significant coronary disease is suggestive of CMD. We speculate that this is the consequence of prolonged systemic inflammation, which may precede and contribute to premature coronary artery disease in these patients.