In anaesthetized open-chest casts with occlusion of the left anterior descending coronary artery (LAD), adenine nucleotides and degradation products were studied in small myocardial tissue samples (10-20 mg) with high-pressure liquid chromatography, and tissue blood flow was measured with radioactive microspheres 5, 10, 20, 40, and 60 min after LAD occlusion. There was a rapid and parallel decrease of myocardial ATP and accumulation of adenosine, inosine, hypoxanthine, and xanthine both in epicardial and endocardial half-layers of the ischaemic myocardium within the first 20 min of coronary occlusion. After 40 and 60 min, myocardial ATP content decreased and degradation products accumulated further in the endocardium but stabilized epicardially. Analysis of covariance showed that the slightly higher blood flow in ischaemic epicardial layers, did not explain the transmural difference in ATP content after 40 and 60 min. Adenosine decreased after 40 min of ischaemia in both wall layers reaching negligible amounts after 60 min. It is concluded that breakdown of energy stores is less severe in epicardial than in endocardial wall layers during the first hour after acute coronary occlusion in the cat heart. This transmural difference cannot be explained entirely by less severe epicardial ischaemia. Therefore, transmural heterogeneity in metabolic function during severe ischaemia may also be important.