The electrophysiological effects of varying concentrations of mexiletine on isolated rabbit sinus node and atrial preparations. Purkinje fibres, Purkinje-fibre-ventricular muscle junction and distal conduction system ('gate') were studied in oxygenated Tyrode solution at 35 degrees C using standard microelectrode techniques. 'Therapeutic' concentrations of mexiletine (0.5 to 2.0 micrograms.cm-3) had little effect on the atrial action potentials or on sinus node automaticity but sino-atrial conduction was delayed. In Purkinje fibres, these concentrations of the drug depressed the dV/dtmax of phase 0, conduction velocity and membrane responsiveness accompanied by significant shortening of the action potential duration and the effective refractory period, the change in the former always being greater than that in the latter. Mexiletine decreased antegrade as well as retrograde conduction at the Purkinje-fibre-ventricular muscle junction, while producing a uniform shortening of the action potential duration in the distal conduction system without a preferential effect at the 'gate'. The mechanisms of antiarrhythmic actions of mexiletine are thus complex but resemble those of lignocaine in superfused isolated cardiac muscle.