Limitation of infarct size (IS), using ST-261, was evaluated in a group (I) of eight dogs, during acute MI. Another group (II) served as the control group. The protocol for both groups was the same except that each dog in the treated group was ST-261 as a single bolus (25 mg/kg, in 20ml normal saline), before inducing an occluding thrombus in the mid-LAD, using a closed-chest model, under x-ray visualization. Percentages of total (gms) myocardium at jeopardy (TMJW) and myocardial necrosis (TMNW), delineated by fluoroscein and TTC dyes, respectively, were calculated and compared to the total ventricular myocardial weight (TVMU), by computer technique for both groups at 3 Hrs post-occlusion of the LAD. Mean serum total CPK (CPK-t) and isozymes (mb-band) were measured before and up to 3 Hrs post-occlusion, as were various hemodynamic and mean precordial (21 lead) ST-segment and T-wave amplitudes. There was 14% less TMJU (p<0.05) and 41% less TMNW (p<0.01) in Group I compared to Group II. The mean % of CPK-mb/CPK-t decreased in I and increased in II over the 3 Hrs of observation. Mean HR decreased (p<0.01) in I compared to II at 3 Hrs postocclusion. The sum of the mean T-wave amplitudes from the precordial electrode sites was less in I at 3 Hrs. It is felt that ST-261 had a protective effect on the myocardium during acute myocardial infarction.