The relation between the effect of vasodilator prostaglandins on ventricular arrhythmias during myocardial infarction and infarct size was studied in conscious dogs. Two infarct-limiting drugs, nitroglycerin and ibuprofen, were also studied for comparison. Infusions were given between 20 and 380 minutes after occlusion of the left circumflex coronary artery: intravenously for saline (N = 27), ibuprofen (N = 14), and nitroglycerin (N = 14); left atrially for PGE1 (N = 11), PGE2 (N = 12) and PGI2 (N = 18). Doses of prostaglandins and nitroglycerin were adjusted to decrease mean arterial pressure by 5%. Pathologic infarct size was measured 2 days post-occlusion. During the infusion period, ventricular fibrillation (VF) deaths were nil with PGI2 (p less than 0.05) and nitroglycerin (p less than 0.1), ventricular premature beats (VPB's) were less (p less than 0.01) with PGI2, PGE2 and nitroglycerin, and collateral blood flow (microspheres) increased with PGE1, PGI2 and nitroglycerin but did not change with saline, PGE2 and ibuprofen. Infarct size, as percent of left ventricle or occluded bed, was less (p less than 0.05) with PGE1, PGI2, nitroglycerin and ibuprofen but similar with PGE2 and saline. Thus, PGE2 diminished VPB's despite no effect on flow or infarct size. In contrast, both PGE1 and PGI2 diminished VPB's, increased flow and decreased infarct size, but PGI2 also reduced VF mortality.