The fundamental abnormality in syndrome X (angina pectoris, ischaemia-like stress ECG despite angiographically normal coronary arteries) might be patchily distributed increased tone in pre-arteriolar coronary vessels with compensatory release of adenosine. The aim of this study was to confirm this hypothesis and to explore its relationships with autonomic system functioning. Using parametric positron emission tomography, myocardial perfusion was examined in 480 segments in 16 syndrome X patients and 16 age- and sex-matched healthy volunteers. Autonomic function was explored by Holter monitoring of time domain parameters of heart rate variability. Compared to volunteers, both mean perfusion (123 +/- 35 vs 87 +/- 16 mg.min-1.100 g-1; P < 0.01) and its coefficient of variation (17.0 +/- 3.2 vs 13.6 +/- 2.2%; P < 0.01) as a measure of perfusion heterogeneity, were higher in patients with syndrome X. In contrast to the findings in the control subjects, patients showed an inverse relationship between perfusion heterogeneity (coefficient of variation of segmental perfusion) and autonomic tone (heart rate variability parameters). Since marked perfusion heterogeneity (inversely related to autonomic tone) and higher overall perfusion were found, the study supports the data that in syndrome X hyperreactivity of small coronary vessels with compensatory release of adenosine may be patchily distributed.