The pharmacokinetics, safety, and tolerability of four topical lidocaine patches 5% continuously applied for 72 hours and changed every 12 or 24 hours were examined. In this randomized, prospective, multiple-dose, open-label pharmacokinetic study, lidocaine patches were applied to healthy men and women for three consecutive days. Ten subjects received four lidocaine patches every 24 hours (group 1), and 10 subjects received four patches every 12 hours (group 2). Serial samples of venous blood were obtained to determine pharmacokinetic data. Overall tolerability and safety were assessed, and skin sensory testing was conducted to determine whether local anesthetic activity was produced. The mean maximum plasma lidocaine concentrations at steady state with lidocaine patches applied in groups 1 and 2 were 186 and 225 ng/mL, respectively, compared with the reported mean maximum plasma concentration of 130 ng/ml. with the labeled dosage (12 hr/day). The area under the concentration-time curve for one dosage interval at steady state was 3550 and 4506 ng.hr/mL for groups 1 and 2, respectively. No loss in sensation at the application site was reported. No patient had edema, and most cases of erythema were very slight. No systemic adverse events were judged to be related to the patches. Continuous application for 72 hours of four lidocaine patches 5%, changed every 12 or 24 hours, produced plasma lidocaine concentrations that remained well below those that typically produce antiarrhythmic effects or toxicity. Mild application-site erythema occurred in most patients, but no systemic adverse reactions were judged to be related to the patches. No loss in sensation at the application site was reported.