Substitution of a methyl group at one or both of the ortho-positions of the benzene ring in procaine amide and procaine provides analogs that are more active in prolonging the refractory period of isolated rabbit atria than procaine amide itself. These analogs, however, fail to abolish ouabain-induced ventricular and aconitine-induced atrial arrhythmias in cats. On the other hand, analogs like 2-diethylamino-4′-amino-2′,6′-dimethylacetanilide dihydrochloride monohydrate, 4-amino-N-(2-diethylaminoethyl)-2′, 6′-dimethylbenzamide, 2-diethylaminoethyl 4-amino-2-methyl-benzoate, and 2-diethylaminoethyl 4-amino-2,6 − dimethylbenzoate produce a significant increase in the amount of ouabain required to elicit ectopic rhythm in cats when administered before the infusion of the glycoside. Of these four compounds, the last three also show local anesthetic activity in the corneal reflex test in rabbits. Reversal of the amide group in procaine amide significantly reduces the activity in prolonging the refractory period of cardiac tissue and does not seem to improve the antiarrhythmic activity of the parent compounds.