Background The effect of acute hyperglycemia (AHG) during the oral glucose tolerance test (OGTT) on coronary microvascular function was evaluated, as well as the associations among the changes in coronary microvascular function, oxidative stress, and sympathetic tone. Methods and Results Transthoracic Doppler echocardiography and OGTT were performed in 24 subjects with atherosclerotic risk factors (61±9 years). The coronary flow velocity before and during the infusion of adenosine (CFV_hyp), plasma levels of thiobarbituric acid-reactive substances (TBARS), and the low-frequency/high-frequency power (LF/HF) ratio yielded by power spectral analysis of heart rate variability were measured before and at 1 h during 75-g OGTT. AHG significantly decreased the CFV_hyp, and increased the TBARS and LF/HF. Multiple linear regression analysis revealed that the percent changes in the CFV_hyp were significantly associated with the percent changes in the LF/HF ratio (β=-0.43, p<0.05). Conclusion In subjects with atherosclerotic risk factors who may be considered likely to have atherosclerotic arterial damage, AHG seems to induce concomitant coronary microvascular dysfunction, increased oxidative stress, and sympathetic activation. Coronary microvascular dysfunction, therefore, appears to be closely related to sympathetic activation. (Circ J 2007; 71: 202 - 206)