A study of the efficacy, toxicity and pharmacokinetics of lidocaine was performed to determine 1) the maximal number of bolus injections that can be given every 5 minutes to suppress complex ventricular arrhythmias in apparently refractory patients, 2) the influence of left ventricular failure on the time course of lidocaine plasma concentrations, and 3) the relation of plasma drug concentration during bolus loading and observed effects. Twenty-one patients participated in this study (15 with acute myocardial infarction and 6 with prolonged coronary insufficiency). Nine patients had severe left ventricular failure (pulmonary edema or shock, or both) and two had moderate failure. All patients received an initial 75 mg bolus dose (all doses were infused at 50 mg/min) followed at 5 minute intervals by 50 mg supplementary bolus doses until complex arrhythmias were abolished or signs of toxicity were observed. Nineteen of 21 patients who failed to respond (abolition of all complex arrhythmias and reduction of total ectopic beats to <5/min) to the maximal standard loading dose (225 mg in a 16 minute period) responded favorably to a total loading dose of 275 to 375 mg. Furthermore, toxicity was confined to six episodes of mild severity (numbness of lips or tongue, mild sleepiness) and two episodes of moderate severity (agitation, somnolence, nausea). After the first bolus, it was observed that patients with moderate-severe left ventricular failure exhibited higher plasma concentrations than did patients without left ventricular failure. However, this difference was not sustained when the loading doses exceeded 175 mg. The data suggest that a total loading dose of 375 mg may be given if necessary over 31 minutes to patients refractory to conventional doses, including patients with severe left ventricular failure , and that many “lidocaine resistant” patients have a quantitative, not qualitative, difference in the sensitivity of their arrhythmia to this drug.