Abstract: From animal studies, it is known that the suppression of motor reactions after painful stimuli, i.e., the MAC, is mediated at a subcortical site. To confirm these findings in humans, we studied the concentration-dependent effect of sevoflurane and propofol on electrophysiological parameters derived from either the spinal cord (H-reflex and F-waves) or the cerebral cortex (EEG). A total of 161 patients were studied with either sevoflurane or propofol and either H-reflex or F-wave measurement. In parallel, EEG parameters were recorded. The hysteresis between anaesthetic concentration and effect was eliminated by calculating the time constant t 1/2ke0 for equilibration between plasma and effect compartment, using pharmacokinetic–pharmacodynamic modelling. Equilibration time constants t 1/2ke0 were much larger for spinal parameters than for the EEG parameters, both for sevoflurane and propofol. For sevoflurane, the concentration–response curve for H-reflex suppression was similar to the logistic regression curve for suppression of movement, whereas F-waves were suppressed at much lower concentrations. The differences in equilibration time constants between EEG parameters and spinal parameters are in line with the findings in animal experiments that suppression of movement by anaesthetics occurs at a site distinct from those causing EEG alterations and presumably unconsciousness. [Copyright &y& Elsevier]