Isolated, buffer perfused guinea pig hearts were used to study the effects of sotalol on arrhythmias and electrophysiology during 30 min of myocardial ischaemia, induced by reducing coronary flow to 10% of control, and subsequent reperfusion. Action potentials were recorded using the floating microelectrode technique and arrhythmias were noted and defined by extracellular electrical records. Sotalol 10(-4) mol X litre-1 reduced the incidence of ventricular arrhythmias during myocardial ischaemia and reperfusion. Prior to the onset of ischaemia sotalol reduced action potential amplitude and Vmax, and prolonged action potential duration, refractory period, and conduction time, and increased pacing threshold. During myocardial ischaemia the effect of sotalol on action potential duration disappeared, and that on refractory period was diminished. The effect of sotalol on action potential amplitude and Vmax was reduced during the early (2 to 12 min) part of ischaemia, but later, at the onset of arrhythmias, tended to reemerge, while the effect on QRS width was exaggerated. Thus the cellular electrophysiological effects of sotalol on normal myocardium provided a poor guide to the mechanism of its antiarrhythmic action in ischaemic tissue.