PURPOSE: This study investigates the interactions between midazolam premedication and propofol infusion induction of anesthesia for multiple anesthetic endpoints including: loss of verbal contact (LVC; hypnotic), dropping an infusion flex (DF; motor), loss of reaction to painful stimulation (LRP; antinociceptive) and attainment of electroencephalographic burst suppression (BUR; EEG). METHODS: In a double blind, controlled, randomized and prospective study, 24 ASA I-II patients received either midazolam 0.05 mg x kg(-1) (PM; n = 13) or saline placebo (PO; n = 11) i.v. as premedication. Twenty minutes later, anesthesia was induced by propofol infusion at 30 mg x kg(-1) x hr(-1). ED50, ED95 and group medians for times and doses were determined and compared at multiple anesthetic endpoints. RESULTS: At the hypnotic, motor and EEG endpoints, midazolam premedication significantly and similarly reduced propofol ED50 (reduction: 18%, 13% and 20% respectively; P <0.05 vs unpremedicated patients) and ED95 (reduction: 20%, 11% and 20% respectively; P <0.05 vs unpremedicated patients). For antinociception (LRP), dose reduction by premedication was greater for propofol ED95 (reduction: 41%; P <0.05 vs unpremedicated patients) than ED50 (reduction: 18%; P <0.05 vs unpremedicated patients). Hemodynamic values were similar in both groups at the various endpoints. CONCLUSIONS: Midazolam premedication 20 min prior to induction of anesthesia reduces the propofol doses necessary to attain the multiple anesthetic endpoints studied without affecting hemodynamics in this otherwise healthy population. The interaction differs for different anesthetic endpoints (e.g., antinociception vs hypnosis) and propofol doses (e.g., ED50 vs ED95).