The distal 1 3 of the anterior descending branch of the left coronary artery in 33 pentobarbital-anesthetized dogs was ligated, and subsequently fresh-frozen, cold microtome sections of ventricular myocardium were studied for enzymatic activity. The state of dehydrogenase activity correlated morphologically with severity of local ischemia: destruction of architecture was accompanied by loss of enzymatic activity while unaltered myocardium was characterized by a "fine-dot" pattern of enzyme staining. These dots were interpreted as moderately stained mitochondria measuring up to 1 μ in diameter and 2 μ in length. In a third intermediate zone completely separating the first 2, a "large-dot" pattern appeared which was interpreted as resulting from mitochondria which were swollen to twice the normal size and more intensely stained. Stains for all 8 dehydrogenase enzymes studied responded similarly to the circulatory embarrassment. A-band swelling and accumulation of neutral-fat droplets were observed in this third zone but the architecture was otherwise undisturbed. The comparative size of the respective zones varied with the duration of the ischemic insult. Six hours after ligation, only the normal and intermediate zones were found, but as architectural deterioration developed, the size of this ischemic region gradually shrank to less than half of the abnormal myocardium. The injured region reached its maximum at 18 hours and subsequently regressed until 24 hours, after which it remained relatively constant. The zone of myocardial ischemia as identified by altered dehydrogenase staining remains to be characterized as to its functional capacity with regard to either electrical or mechanical activity.