Serum concentrations of pro cain amide (PA) and N-acetylprocainamide (NAPA) were measured by fluorometry in subjects with normal renal function (n = 4) and in patients with end-stage renal failure (n = 3) after administration of 6.5 mg/kg of PA · HCI orally. Two subjects with normal renal function were rapid isonicotinic acid hydrazide (INH) acetylators and two were slow acetylators. The rapid acetylators had higher peak serum levels of NAPA (1.80 µg/ml) than the slow acetylators (0.40 µg/ml). Peak serum levels of PA were essentially identical in both. The half-life (T½) of PA was shorter, 2.5 hr, in the rapid acetylators than in the slow, 4.1 hr. The slope of the terminal portion of the blood time curve for NAPA was steeper (−0.087) for slow acetylators than for rapid (−0.078). These apparent differences between rapid and slow acetylators are not conclusive in themselves but tend to support the differences in acetylation previously reported. In the absence of renal function, the serum levels of PA were higher and the T½ prolonged. The serum levels of NAP A rose slowly and reached peak levels of 2 to 3 µg/ml and declined only with hemodialysis. In 3 patients measurable levels of NAPA were still present 78 hr (0.62 µg/ml), 94 hr (0.36 µg/ml), and 124 hr (0.70 µg/ml) after the single oral dose of PA. Clearance of NAPA during clinical hemodialysis was 48 ± 10 cc/min compared to 75 ± 12 ml/min for PA.