The effects of intracellular and extracellular application of bretylium tosylate on outward potassium current and fast inward Na+ current have been studied in single ventricular cells of chick embryo (18-day-old) using the whole-cell voltage clamp technique. Extracellular superfusion with bretylium (3 x 10(-4) M) decreased the K+ current (IK) whereas the fast INa remained unaffected. Introducing bretylium intracellularly also decreased IK, but rapidly inhibited the fast INa. The addition of 3 x 10(-4) M bretylium to the superfusion medium in the presence of intracellular bretylium further decreased IK and caused the fast inward sodium current (INa) to recover. The decrease of IK by bretylium may account for the antifibrillatory properties of this drug in heart.