Midazolam and fentanyl together produce better sedation, analgesia and amnesia than do either drug alone, but the electrophysiologic effects of the combination are unknown. Twenty patients undergoing electrophysiologic studies for clinical reasons were studied. Blood pressure, heart rate, respiratory rate, oxygen saturation, and standard variables related to atrioventricular and ventriculoatrial conduction, dual pathways, accessory pathway conduction, sinus node function, and the inducibility of tachycardia were examined before and after intravenous injections of midazolam (0.07 +/- 0.03 mg/kg) combined with fentanyl (0.8 +/- 0.4 micrograms/kg). There were no significant changes in the electrophysiologic variables or ease of inducibility of tachycardia. The drugs were well tolerated; they produced minor and clinically unimportant reductions in mean blood pressure (99 +/- 13 to 89 +/- 16 mm Hg; p < 0.001) and respiratory rate (18 +/- 4 to 16 +/- 3 breaths/min; p = 0.05). Excellent sedation was achieved. Major amnesia was reported by 95% of patients. In conclusion, midazolam combined with fentanyl provides safe and effective sedation for electrophysiologic studies without significantly affecting electrophysiologic variables or the inducibility of tachyarrhythmias.