Antiarrhythmic agents can influence defibrillation threshold (DFT). Basic research suggests that some class I drugs may have deleterious effects by raising defibrillation energy requirements. Evaluation of this problem in man has been limited to reports of patients who were more difficult to cardiovert or defibrillate after treatment with amiodarone and class IC agents. In the present report, mexiletine appeared to be the probable cause of an important elevation of DFT in a patient undergoing replacement of a malfunctioning automatic implantable cardioverter/defibrillator (AICD). This report and the accompanying literature review suggest that more information at both the basic and clinical levels is required. Retesting of device efficacy in terminating induced arrhythmia in the laboratory appears prudent in patients who require antiarrhythmic drug therapy subsequent to AICD implantation.