The acute intravenous cardiovascular toxicity of five amide local anesthetic agents was studied in intact, ventilated dogs anesthetized with pentobarbital. Minimal changes in various cardiovascular functions were seen at doses of 0.3 to 3.0 mg/kg. At 10 mg/kg profound hypotension accompanied by significant decreases in cardiac output and stroke volume were observed with etidocaine and bupivacaine. At this dose lidocaine, mepivacaine, and prilocaine produced moderate signs of cardiovascular depression. Myocardial depression appeared to be primarily responsible for the profound hypotension, as minimal changes in peripheral vascular resistance occurred except as a terminal event. Pulmonary vascular resistance tended to increase before myocardial depression, suggesting a pulmonary vasoconstrictor action of the anesthetics. The cumulative lethal dose varied from approximately 80 mg/kg for lidocaine and mepivacaine to 40 mg/kg for etidocaine and 20 mg/kg for bupivacaine. The acute cardiovascular toxicity of these agents is proportional to their comparative in vivo anesthetic potency which indicates little difference in therapeutic ratio between the various amide local anesthetics.