Upon finding 2-(α,α,β,β-tetrafluorophenethyl)benzylamine (4) to be a potent and novel type of antiarrhythmic agent, the title compounds were synthesized. Structure-activity relationships in this series are described. Among the current drugs for the treatment of cardiac arrhythmias are quinidine and procaine amide, which exhibit similar pharmacologic and electrophysiologic activities. They also share similar disadvantages, especially in terms of myocardial depression. Lidocaine, on the other hand, differs quantitatively in its appreciably less marked alteration of the electrophysiologic properties of the heart. However, it is rapidly metabolized, is usually administered by continuous intravenous infusion, and can cause adverse central nervous system side effects. In the belief that a clinically effective antiarrhythmic agent does not also have to have toxic symptomology, we undertook a search for a nonquinidine type of active structure. This screening program provided a synthetic lead to 2-(α,α,β,β-tetrafluorophenethyl)benzylamine (4), a potent and novel compound. A study pursued to delineate the structure-activity relationships of a series of 2-, 3-, and 4-(α,α,β,β-tetrafluorophenethyl)benzylamines is described.