OBJECTIVE To determine whether, following aerosolization of lidocaine for topical airway anesthesia, intravenous (IV) lidocaine produces toxic lidocaine blood concentrations. METHODS Randomized, double-blind study. METHODS University-affiliated hospital. METHODS Forty healthy patients scheduled for outpatient surgery. METHODS The patients received in a randomized, double-blind manner aerosolized lidocaine or placebo followed 10 minutes later by IV lidocaine or placebo. RESULTS After completion of lidocaine or placebo aerosolization and 2 minutes following IV administration of either lidocaine or the placebo, venous blood samples were obtained. Lidocaine concentration was measured using a homogenous enzyme assay. The group receiving both aerosolized and IV placebo and the group receiving aerosolized lidocaine and an IV placebo had undetectable (less than 0.05 micrograms/ml) serum lidocaine levels. The groups that received either an aerosolized placebo or aerosolized lidocaine and IV lidocaine had similar serum lidocaine concentrations [3.34 +/- 0.46 vs. 3.24 +/- 0.55 micrograms/ml (mean +/- SEM); p greater than 0.05 by Mann-Whitney U test]. CONCLUSIONS IV lidocaine can be safely administered following aerosolization of lidocaine in spontaneously breathing patients without producing toxic blood lidocaine concentrations.