The present investigation was carried out in anesthetized dogs to compare the cardiovascular effects of dopamine and monensin, a carboxylic ionophore, in normal and E coli endotoxin-induced shock conditions. In control animals, monensin increased cardiac contractility, cardiac output, systemic blood pressure, and coronary blood flow in a dose-dependent manner, but had little or no effect on heart rate. However, unlike dopamine, which selectively increased renal blood flow, monensin did not affect renal blood flow in doses that produced a maximal increase in coronary blood flow or other hemodynamic effects. The duration of action of monensin was longer than 2 hr. Both dopamine and monensin reversed the cardiac depression and hypotension produced by E coli endotoxin, and in these experiments also, the duration of action of monensin was longer than 2 hr. Regional blood flow measurements with the radioactive microsphere (15 mu) technique demonstrated a marked decrease in organ blood flows at 60 min postendotoxin, but some recovery was observed at 90 min. In the left ventricle, reduction of flow to the endocardial region was greater than to the epicardium. In dogs with endotoxic shock, monensin produced a significant increase in organ blood flows towards or even above control values.