Although electroencephalogram reactivity (i.e. transient changes in electrical brain activity following external stimulus) might be useful in depth-of-anaesthesia monitoring, it has not been systematically examined with different anaesthetics at doses titrated to unresponsiveness. Three 10-subject groups of healthy volunteers received dexmedetomidine, propofol or sevoflurane in escalating pseudo-steady-state concentrations at 10-min intervals until they did not open their eyes to command. The electroencephalogram was continuously recorded and spectral variables were calculated with short-time Fourier transform and time-varying autoregressive modelling. ⋯ Dexmedetomidine, propofol and sevoflurane induced distinct suppression patterns on the electroencephalogram reactivity at the same clinical endpoint (unresponsiveness). Reactivity was best maintained with propofol, while only minimally preserved with dexmedetomidine and sevoflurane. Thus, it may be difficult to harness reactivity for depth-of-anaesthesia monitoring.