Whole-cell recordings in voltage-clamp mode were performed on acutely isolated neurones from rat neocortex and neostriatum to examine the effects of the anticonvulsant phenytoin on a non-inactivating (persistent) Na+ current (INaP). INaP was chosen because it enhances neuronal excitability near firing threshold, which makes it a potential target for anticonvulsant drugs. In both preparations, phenytoin (10-100 microM) inhibited INaP in a dose-dependent fashion without altering the voltage-dependence of current activation. On average, half-block of INaP was produced by 34 microM phenytoin suggesting that therapeutic drug concentrations are likely to affect INaP. Inhibition of INaP might represent a novel mechanism contributing to the anticonvulsant profile of phenytoin.