This paper reports the cardiovascular effects of intentionally toxic intravenous doses of lidocaine, bupivacaine, and ropivacaine and the mechanisms of death. Fatal doses of lidocaine, bupivacaine, and ropivacaine were established in sheep treated with successive daily dose increments of each drug. The mean fatal dose of lidocaine (+/- SD) was 1450 +/- 191 mg (30.8 +/- 5.8 mg/kg), that of bupivacaine was 156 +/- 31 mg (3.7 +/- 1.1 mg/kg), and that of ropivacaine was 325 +/- 108 mg (7.3 +/- 1.0 mg/kg); thus the ratio of fatal doses was approximately 9:1:2. In four out of four lidocaine-treated animals, respiratory depression with bradycardia and hypotension without arrhythmias were the causes of death. Three out of four bupivacaine-treated animals died after the sudden onset of ventricular tachycardia/fibrillation without hypoxia or acidosis; the fourth died in a similar manner to the lidocaine-treated animals. Three out of five animals given ropivacaine died in a manner resembling the fatal effects of lidocaine-treated animals, but unlike the lidocaine-treated animals, in all three sheep there were also periods of ventricular arrhythmias. The remaining two ropivacaine-treated sheep died as a result of the sudden onset of ventricular tachycardia/fibrillation. The mean percentages of the fatal dose found in the myocardium was 2.8 +/- 0.7 for lidocaine- treated animals, 3.3 +/- 0.9 for bupivacaine-treated animals, and 2.2 +/- 1.4 for ropivacaine-treated animals; the corresponding percentages in whole brain were, respectively, 0.71 +/- 0.01, 0.71 +/- 0.21, and 0.89 +/- 0.27.