A liquid chromatographic method for the determination of procainamide (PA) and N-acetylprocainamide (NAPA) in serum has been developed. This method utilizes isocratic conditions, ambient temperature, and a conventional fixed-wavelength 280-nm detector. Sample pretreatment involves extraction of PA and NAPA, along with p-amino-N-(2-dipropylaminoethyl)-benzamide hydrochloride as internal standard, into an organic phase and reextraction into an aqueous acidic phase. Using this sample pretreatment, interferences due to commonly used drugs are eliminated. The method accurately measures PA and NAPA to levels as low as 1 mg/L.