The effects of ketamine, etomidate, alphaxalone and alphadolone acetate on nodal sodium and potassium currents of frog myelinated nerve fibre have been examined. The four general anaesthetics reversibly depressed ionic currents, although they tended to be more effective in blocking potassium than sodium current. The potassium current was reduced by etomidate and alphaxalone in a time-dependent manner. This was not found for ketamine and alphadolone acetate. In addition to blocking effects on sodium current, etomidate, alphaxalone and alphadolone acetate, but not ketamine, induced a negative shift of steady-state sodium inactivation-voltage curves. Collectively, the general anaesthetics appeared to alter specifically and differentially sodium and potassium channel-gating systems. The simplest interpretation of these results suggests that the compounds produce state-dependent blocks of ionic channels, and that there are general anaesthetic receptor sites located on the channel proteins themselves. Furthermore, potassium and sodium channels may contain several types of receptor sites, through which anaesthetics could exert their different actions.