Patients with syndrome X have been found to have an abnormal coronary blood flow reserve. The physical performance during exercise, however, has been incompletely investigated. Cardiopulmonary exercise testing (CPX) is a reliable noninvasive method to provide indexes of lung, heart, circulation, and muscle functions. In 15 patients (10 women) with syndrome X and in age and sex-matched normal individuals, CPX was performed twice a day (8 AM and 4 PM) on two separate occasions 2 months apart. Time and oxygen consumption at peak exercise, at ventilatory anaerobic and electrocardiographic thresholds, as well as norepinephrine plasma concentrations at each work load and at peak exercise in both tests were obtained. In syndrome X in both evaluations, the 4 PM performance was characterized by an earlier onset of both ventilatory anaerobic and electrocardiographic thresholds despite lower values of VO2 and double-product, and by a greater peak ST segment depression despite similar total exercise time, VO2, and double-product. No difference between tests was found in the norepinephrine response to exercise. Normal subjects showed reproducible CPX and hormonal responses in the two tests. Thus these data may suggest a circadian variation of coronary vascular response to exercise in patients with syndrome X, leading to a lower ischemic threshold early in the afternoon. The parallel earlier onset of the ventilatory anaerobic threshold may reflect a concomitant abnormal muscular blood flow response (that is, vasoconstriction of working muscle arteries), suggesting a link between coronary and peripheral circulations.