To test the hypothesis that the relationship between infarct area (IA) and area at risk (AR) varies in different layers of the left ventricle (LV), we occluded the circumflex coronary artery for 48 h in 20 conscious dogs. AR was determined by postmortem coronary stereoarteriography, and infarct area by pathological examination. Both AR and IA were divided into four layers: posterior papillary muscle (PPM), subendocardium (Endo), midwall, and subepicardium (Epi) and quantified with planimetry. Hemodynamics and regional myocardial flow with tracer microspheres (7-10 micrometers diam) were measured before and after coronary occlusion. IA was closely correlated with AR for PPM (r = 0.96), Endo (r = 0.97), and Epi (r = 0.92). However, the slope of IA/AR for Endo (1.30 +/- 0.08) was significantly steeper (P less than 0.05) than that for Epi (0.89 +/- 0.11); furthermore, the intercepts at zero infarction for PPM (0.5 +/- 0.1% of LV), Endo (4.2 +/- 0.4%), and Epi (0.1 +/- 0.7%) were significantly different from each other. Regional blood flow measurements indicate that the differences in IA/AR in various layers reflected earlier and greater total collateral flow to the noninfarcted AR in the epicardium. Thus IA/AR for the entire LV is a composite representing separate IA/AR specific to various transmural layers of the LV. In addition, this study demonstrates that the lateral border zone between the IA and the AR is minimal (less than 3-5 mm) in the subendocardium and midwall layers of the left ventricle.