Pharmacokinetics of procainamide were studied in healthy volunteers after single doses intravenously and orally as conventional and slow-release tablets and after repeated oral doses to steady state. The initial distribution after intravenous administration was rapid and the overall elimination in the ß-phase corresponded to tÛ of 2.7 hr. The mean volume of the central compartment was small and only 4% of Vd(ß), which was 2.3 l/kg body weight. About 65% was excreted unchanged after intravenous administration and about 55% after a single oral dose of 500 mg. The recovery of the metabolite N-acetylprocainamide was 12% after both routes of administration. Procainamide was completely absorbed from the gastrointestinal tract and the first-pass elimination was very limited. The rates of absorption from the tablet compositions were weil correlated to the in vitro dissolution properties. Administration of slow-release tablets every 8 hr gave about the same mean plasma level at steady state as ordinary tablets given every 4 hr, and the availability was the same from both preparations. The occasional high plasma concentration peaks after ordinary tablets were not observed after the slow-release tablets. Renal clearance was about 500 ml/min, indicating an active secretion in the tubules.