In search of a molecular site and mechanism of action for anaesthetics, we have examined the effects of racemic ketamine on single human CNS sodium channels with the new planar lipid bilayer technique. In the dose range studied (0.05–9.2 mmol litre−1) ketamine depressed in a dose-dependent manner two major functions of the sodium channel, by reducing the fractional open time in a voltage-independent manner (ED50 1.1 mmol litre−1; maximal conductance block 71 %) and by interfering with the voltage-dependent, steady-state activation. These actions occurred at concentrations which were greater than those used clinically in general anaesthesia (up to 0.02 mmol litre−1), therefore they reflect local rather than general anaesthetic effects which may be related to the hydrophobic properties of ketamine. In comparison with two other i.v. anaesthetic agents, pentobarbitone and propofol, racemic ketamine behaves differently at both the molecular and the clinical level.