To evaluate age-dependent changes in lidocaine disposition in patients with acute myocardial infarction, we measured plasma concentrations of lidocaine and its metabolites monoethylglycinexylidide and glycinexylidide after discontinuation of a maintenance lidocaine infusion. Plasma lidocaine clearance was calculated by dividing the lidocaine concentration at the end of the infusion into the maintenance infusion rate. Lidocaine clearance in 35 patients was related to body weight and was reduced by heart failure. Heart failure was more common in the elderly, occurring in 15 of 27 (56%) patients over 65 years old and seven of 29 (24%) patients under 65 years old. There was a reduction in lidocaine clearance with age due, in part, to lower body weight and a higher prevalence of heart failure in the elderly. Multilinear regression analysis showed that age and weight contributed to the prediction of lidocaine plasma clearance in patients with and without heart failure. Age was a particularly important predictor of lidocaine clearance in patients with heart failure. Adjustment of lidocaine maintenance doses based on age, weight, and heart failure may help control the frequency of lidocaine adverse reactions in the elderly.