Using voltage-clamp technique, the influence of two structurally different neuroleptics haloperidol and chlorpromazine on Na+ transport in frog skin was investigated. It was shown for the first time that haloperidol and chlorpromazine modulate the transepithelial Na+ transport. The results obtained also suggest that the regulatory effect of these antipsychotic agents on Na+ transport in frog skin is mediated by distinct signaling mechanisms.