The effect of a single dose (10 mg/kg) of intravenous thiopental (TP), during acute myocardial infarction, on infarct size was studied in conscious dogs randomized 10 minutes after left circumflex coronary artery occlusion to either the TP group (n = 10) or a control group given 0.9% saline solution (n = 10). During the first hour following therapy, myocardial blood flow (microspheres), arterial pressure, left atrial pressure, and arterial blood gases were similar in the two groups, but the heart rate (140 +/- 3 vs 110 +/- 3 bpm; p less than 0.001) and rate-pressure product (15,090 vs 12,210 bpm X mm Hg; p less than 0.025) were greater in the TP group. Infarct size (planimetry) and occluded bed size (postmortem coronary arteriography) measured 2 days later revealed that: the slope of the relation between infarct and occluded bed mass, as a percentage of the left ventricle (% LV) was greater with TP than with saline solution (1.10 vs 0.61; p less than 0.001); excluding hearts (four TP and three saline solution) with small occluded beds (less than 22% LV), infarcts were also larger with TP (n = 6) than with saline solution (n = 7), both as a percentage of the left ventricle (26.4 vs 12.2%; p less than 0.02) or occluded bed (61.5 vs 28.9%; p less than 0.005); and transmural and endocardial extents of the infarcts on topographic maps were greater with TP than with saline solution. In 12 other conscious dogs, increasing the heart rate between 10 and 70 minutes after left circumflex coronary artery occlusion to the average rate of the TP group (140 bpm) by atrial pacing resulted in infarcts larger than those in control dogs but similar to those in the TP group. Thus, TP therapy after left circumflex occlusion increased infarct size in dogs. This effect appeared to be due mainly to the increased heart rate, probably via increased myocardial oxygen demands.