Using the voltage-clamp technique, it has been shown for the first time that the neuroleptic drugs chlorpromazine and trifluoperazine, which act as sigma-1 receptor antagonists, attenuate Na ⁺ transport in the frog skin epithelium. The results suggest that sigma-1 receptors may be involved in the regulation of transepithelial Na ⁺ transport in frog skin.