Seven patients with angina pectoris and 201-thallium scintigraphy indicative of myocardial perfusion defects, but with normal coronary angiograms, were investigated. Metabolic events were studied in biopsies from myocardium and skeletal muscle (m. quadriceps femoris). Profound metabolic derangement was evidenced by a distinctly lowered energy charge in myocardium (0.88 +/- 0.04 in controls vs. 0.48 +/- 0.09 in patients; P less than 0.001) and skeletal muscle (0.92 +/- 0.01 in controls vs. 0.70 +/- 0.09 in patients; P less than 0.01). Accordingly, low values were recorded for ATP in both types of muscle, where ATP was lower than (myocardium) or the same as (skeletal muscle) ADP. The concentration of myocardial lactate was 115 +/- 74 mumol g-1 dry weight and that of skeletal muscle lactate was 11 +/- 3 mumol g-1 dry weight, compared to normal myocardial lactate of 18 +/- 10 mumol g-1 dry weight and normal skeletal muscle lactate of 11 +/- 3 mumol g-1 dry weight. Unprecedentedly low energy charge levels in both cardiac and skeletal muscle biopsies suggest that a systemic metabolic disease is highly probable. An inverse ATP/ADP ratio found in our patients is indicative of an aetiology different from ischaemia, which would not produce this relationship.