The purpose of this study was to determine the effect of the Na+K+ATPase inhibitor sanguinarine on the refractory period of the porcine ventricle. Measurements of ventricular refractoriness and strength-interval curves were obtained before and after 0.5 to 4.0 mg/kg sanguinarine. The ventricular refractory period was found to be prolonged at all doses studied from a control of 276 +/- 12 msec to 318 +/- 24 msec at 4.0 mg/kg (p < 0.01). The strength-interval curve was shifted to increased values for ventricular refractoriness from 0.5 to 16.0 ma. No depression of arterial pressure or left ventricular dp/dt was observed. This study shows that sanguinarine prolongs ventricular refractoriness. This property may be useful in the treatment of ventricular arrhythmias.