Ischaemic preconditioning, with brief periods of ischaemia separated by reperfusion, increases myocardial resistance to infarction. In addition, preconditioning leads to preservation of myocardial adenosine triphosphate (ATP) during ischaemia. We propose that ischaemic preconditioning may share fundamental similarities with intermittent aortic cross-clamping utilised during aorto-coronary bypass surgery. The aim of this study was to test the hypothesis that controlled aortic cross-clamping is a form of preconditioning using conservation of ATP as the end point. Patients randomised to the preconditioned group (preconditioned, n = 10 patients), received a preconditioning stimulus of two 3-min periods of cross-clamping separated by 2 min of reperfusion prior to an ischaemic insult of 10 min ischaemia and ventricular fibrillation. In the control group (control, n = 10 patients) hearts received 10 min cross-clamping with fibrillation without prior preconditioning. Myocardial ATP, creatine phosphate (CP), and lactate were determined from biopsy specimens taken at the onset of cardiopulmonary bypass (A), at the end of preconditioning (B), and at the end of 10 min of ischaemic insult (C). RESULTS expressed as mean +/- SE (mumol/g dry weight). Preconditioning resulted in a significant depletion of the myocardial ATP content (preconditioned, B: 11.7 +/- 0.9 vs A: 19.8 +/- 1.4; P < 0.01). Furthermore 10 min of ischaemia resulted in a significant depletion of ATP in the control patients (control, C: 7.2 +/- 0.3 vs B: 19.5 +/- 1.2; P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)