The relationship of dosage to plasma concentration of procainamide varied greatly among 186 patients. This variation resulted from individual differences in completeness of absorption, distribution space, and elimination rate. Plasma concentrations correlated well with therapeutic and toxic effects. The usually effective antiarrhythmic concentration was 4 to 8 mg/liter; in occasional patients, 8 to 16 mg/liter was more effective. Toxic manifestations were very rare with concentrations of less than 12 mg/liter, but common with concentrations of more than 16 mg/liter. In most patients, procainamide hydrochloride in a daily dose of 50 mg/kg of body weight produces therapeutic plasma concentrations. Three-hour dosage intervals are required to prevent fluctuations of plasma level exceeding 50%. In urgent situations, a parenteral priming dose should be given. In patients with cardiac or renal failure and when usual doses fail or toxic manifestations appear, determinations of plasma levels are useful guides to dosage.