The skin of amphibians and other isolated epithelial systems are classic model objects for the study of ion transport mechanisms through biological membranes. By the ability to transport electrolytes and by the response to certain hormones, the skin and bladder of amphibians are similar to the distal renal tubules, which allow the data obtained on these objects to be used to determine the water and ion transport mechanisms in kidney cells. Sigma-1 receptors are unique ligand-regulated molecular chaperones located in the plasmalemma and endoplasmic reticulum membrane at the boundary with mitochondria. However, the role of sigma-1 receptors in Na+ transport regulation in epithelial systems is not fully understood. In this regard, it was appropriate to study the involvement of sigma-1 receptors in Na+ transport regulation in frog skin. In the experiments, we used the sigma-1 receptor antagonist - the phenothiazine derivative neuroleptic trifluoperazine. Using voltage-clamp technique, we have shown that preincubation of the frog skin with 20 mg/ml trifluoperazine inhibits Na+ transport in frog skin. It was also observed that trifluoperazine inhibitory effect on Na+ transport depended on the application of the agent from the apical or basolateral surface of the skin and was characterized by biphasic short-circuit current changes upon application of trifluoperazine from the skin apical surface. Similar data were obtained by us earlier when studying the effect of another sigma-1 receptor antagonist phenothiazine neuroleptic chlorpromazine on Na+ transport in frog skin. Thus, in this study and earlier we showed that structurally different sigma-1 receptor antagonists modulate transepithelial Na+ transport, indicating the involvement of sigma-1 receptors in regulation of Na+ transport in frog skin epithelium.