Pathophysiologic mechanisms in syndrome X (anginal chest pain, positive exercise stress test, and angiographically normal coronary arteries) have been extensively studied. Recent reports suggest an ischemic origin of the pain to be less probable. Other contributing mechanisms that have been hypothesized are enhanced sympathetic drive or sensitivity or an abnormal muscle metabolism. Our aim in this study was to characterize exercise performance, skeletal muscle characteristics, and sympathetic control of blood flow in patients with syndrome X. Seven female patients aged 50 to 65 years and 5 matched controls were tested. Exercise test was performed according to clinical routine. Plasma catecholamine and blood lactate levels were measured before, during, and after exercise. Autonomic blood flow control was measured plethysmographically in the resting contralateral forearm during isometric handgrip. Muscle biopsy specimens were obtained at rest from the lateral part of Musculus vastus at midthigh. The biopsy samples were investigated for the relative number of different fiber types, phosphagen content, and energy charge, calculated as (adenosine triphosphate + 12 adenosine diphosphate)/[adenosine triphosphate + adenosine diphosphate + adenosine monophosphate]). Exercise capacity was markedly decreased in syndrome X compared with controls (85 ± 14 vs 156 ± 11 W, p <0.0005) and all patients discontinued exercise because of chest pain (Borg CR-10, 5 ± 3). Peak heart rate was lower in syndrome X (150 ± 18 vs 176 ± 7 beats/min, p <0.01), whereas systolic blood pressure and double product did not differ. Peak norepinephrine plasma levels were lower than in controls (11 ± 6 vs 24 ± 13 nmol/L, p <0.04), whereas peak blood lactate levels did not differ. Blood flow increase in the resting forearm during isometric handgrip was similar to that in controls. The proportion of different fiber types, phosphagen content, and energy charge were normal. Thus, patients with syndrome X have a reduced physical exercise capacity but no skeletal muscle abnormalities. Catecholamine hypersensitivity may contribute to their condition.