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Mexiletine is a type 1B antiarrhythmic drug similar to lidocaine. Prolongation of ventricular depolarization has not been previously reported with the usual oral dosage of mexiletine. We describe a patient with renal failure and heart failure on low-dose oral therapy who developed mexiletine toxicity, which was manifested by ECG prolongation of ventricular depolarization. This was confirmed by elevated plasma concentration of mexiletine. This case illustrates that contrary to the usual belief, mexiletine pharmacokinetics are altered by renal failure. It is important to monitor mexiletine therapy by plasma levels in patients with impaired renal function to avoid mexiletine toxicity.