Cutaneous microvascular responses to physiological stimuli are currently being investigated as indices of vascular function and to monitor responses to therapy. We attempted to systematically assess various microvascular cutaneous flow indices in response to reactive hyperaemia in control subjects and in patients with coronary artery disease (CAD), and to correlate these with brachial artery flow-mediated dilation (FMD). Groups of 24 healthy controls and 24 subjects with CAD underwent sequential brachial FMD determination in the dominant arm, and laser Doppler imaging to assess skin blood flow in the contralateral arm in response to reactive hyperaemia induced by cuff inflation and release. Laser Doppler values were expressed as: (a) AUC(5 min) (area under the curve over 5 min of release), (b) time to peak response, (c) % reactive hyperaemia, and (d) peak perfusion ratio. As expected, FMD was attenuated in CAD patients compared with controls (1.85+/-4.29% compared with 4.30+/-4.00%; P=0.05). Percentage reactive hyperaemia (CAD, 294+/-290%; controls, 501+/-344%; P=0.04) and the time to peak response as measured by laser Doppler imaging (CAD, 16.84+/-9.61 s; controls, 9.13+/-4.43 s; P=0.001) were significantly different between the CAD and control groups, while AUC(5 min) and the peak perfusion ratio did not show significant differences. Receiver operator curves for sensitivity/specificity analysis suggested that the time to peak response derived by laser Doppler imaging was superior to FMD for the diagnosis of CAD, with an overall specificity of 91.3% (positive predictive value of 89.4%) and a sensitivity of 73.7% (negative predictive value of 77.6%). In conclusion, laser Doppler-derived indices of microvascular flow do not correlate with conduit vessel responses. However, a time to peak response of >10 s as measured by laser Doppler imaging offers superior specificity for the diagnosis of CAD compared with brachial FMD.