We compared the effects of a therapeutic concentration of disopyramide with those of quinidine and lidocaine on the action potential characteristics and on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential in the same normal Purkinje fiber in which constant impalement was maintained for more than 7 h. All the drugs depressed the steady-state upstroke velocity in the following order of magnitude: quinidine greater than disopyramide greater than lidocaine. Both lidocaine and disopyramide shifted the normalized steady-state curve to more negative membrane potentials indicating a greater depression of upstroke velocity at lower membrane potentials. Quinidine did not shift this curve. Lidocaine abbreviated all phases of repolarization while both disopyramide and quinidine shortened the plateau phase and lengthened the terminal phase of the action potential. The results suggest that the actions of disopyramide on upstroke velocity resemble those of lidocaine, while its effects on action potential duration resemble those of quinidine. The actions of this drug are therefore more complex than previously assumed.