The effects of 4-aminopyridine (4-AP) were studied on isolated papillary muscles from the heart of reserpinized rabbits (at 37 degrees C). The preparations were paced to contract at 0.67 Hz under isometric conditions and the muscle length was adjusted to 95% of the length for optimum force production. Simultaneous recordings of isometric force and membrane potentials were performed. 4-AP (50 microM) increased peak force by approximately 20% of the control and prolonged the action potential by 20%. Higher concentrations of 4-AP (800 microM) resulted in further increments of force and action potential duration (60 and 70% of controls, respectively). Prolongation of the action potential and potentiation of the isometric force was still present one hour after withdrawal of the drug from the perfusate. The results are consistent with the view that 4-AP prolongs the action potential by inhibiting the late repolarizing potassium current. It is suggested that the calcium uptake by the ventricular cell during the prolonged action potential is increased and that this leads to the positive inotropic effect.