We report the expression of voltage-dependent Na+ channels in Xenopus oocytes injected with total RNA isolated from explanted human hearts. The expressed channels demonstrate characteristic voltage-dependent gating, inhibition by tetrodotoxin, and selectivity for Na+. Oocytes injected with sterile water or intentionally degraded RNA had no similar channel activity. The antiarrhythmic agent lidocaine (20 microM) inhibits current flow through the channel in a voltage-dependent fashion. Na+ channels expressed by injection of human cardiac RNA into Xenopus oocytes qualitatively resemble channels in the native tissue.