We investigated the effect of a small dose of midazolam, ketamine, droperidol or lidocaine on the propofol dose required for hypnosis during induction of general anaesthesia. These drugs were randomly administered to 100 patients about to undergo scheduled surgery. Propofol was then infused at a rate of 250 μg kg−1 min−1 and the hypnotic dose to produce hypnosis was evaluated. Midazolam (20 μg kg−1) and droperidol (20 μg kg−1) significantly reduced the mean hypnotic dose of propofol (mean) S.D.) compared with the placebo (43.7 ± 17.8 mg, 61.9 ± 10.6 mg and 72.5 ± 27.7 mg after pretreatment with midazolam, droperidol and placebo, respectively), whereas ketamine (0.1 mg kg−1) and lidocaine (1 mg kg−1) did not significantly affect the hypnotic dose of propofol (63.1 ± 25.6 mg and 65.1 ± 24.8 mg, respectively). Only midazolam when compared with saline administration, (176 ± 66s and 298 ± 126s, respectively), shortened the time to achieve hypnosis. The changes in blood pressure (non-invasive) and heart rate were not significantly different in all groups during the induction of anaesthesia and oro-tracheal intubation. These results raise the possibility that new combinations of central nervous system drugs, such as droperidol and propofol, have a potential to reduce the dose of intravenous anaesthetics, including propofol, that produce hypnosis without significant adverse effects.