Over the past year we have continued our major commitment to research on N-acetylprocainamide (NAPA). This compound is a metabolite of procainamide (PA) that shows promise of being valuable as a antiarrhythmic drug in its own right. NAPA effectively suppresses ventricular arrhythmias in some patients without subjecting them to the same high risk of developing the drug-induced systemic lupus erythematosus syndrome that if a major drawback to long-term PA therapy. In addition, NAPA can be given on a more convenient dosing schedule than PA and does not have negative inotropic actions that PA shares with the other antiarrhythmic drugs that are currently available. Work that we have accomplished in the past year has demonstrated that NAPA is partially deacetylated in man to PA. To this extent, the apparent immunological safety of NAPA may be relative rather than absolute. We also have investigated the N-dealkylation of PA and NAPA to desethyl N-acetylprocainamide (NAPADE), have identified desethyl procainamide (PADE) as a new metabolite of PA, and have determined the antiarrhythmic activity of these compounds in chloroform asphyxiated mice. We are currently completing a pharmacokinetic analysis of the plasma concentration-hypotensive response relationships of NAPA in dogs.