OBJECTIVE To compare four different methods of endotracheal lidocaine administration with respect to the site of administration. METHODS Randomized controlled trial. METHODS University hospital. METHODS Thirty-two female patients (43.6 +/- 11.5 years old) undergoing elective gynecologic operations with an anesthesiologic risk classification not higher than ASA II. All patients gave their written informed consent to participate in the study. METHODS Lidocaine at a dose of 2 mg/kg, diluted with normal saline to a total volume of 10 mL, was administered to eight patients by instilling the drug solution from a 10-mL syringe directly into the outer aperture of the endotracheal tube. All other study patients received lidocaine under bronchoscopic control through the work channel of the bronchoscope either a) deep endotracheally, b) into the right main bronchus, or c) into the right lower lobe bronchus. At 10 points in time after drug administration, blood samples were taken for measurement of lidocaine plasma concentration (using high-pressure liquid chromatography) and blood gas analysis. RESULTS Therapeutic blood concentrations (greater than or equal to 1.4 micrograms/mL) could be achieved and toxic blood concentrations (greater than or equal to 6 micrograms/mL) could be avoided with all methods of administration. No significant difference was found between the different methods with regard to peak concentration, time to peak, onset and duration of therapeutic levels, or relative bioavailability. A significant (p less than .05) decrease in PaO2 to 75% of the baseline was seen with all methods used. CONCLUSIONS Because no route of lidocaine administration was superior to the others, the simplest method (instillation into the endotracheal tube) should be used.