Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were stuudied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320–400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35–55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 ± 0.46 (mean ± SD) μg/ml following the first injection and 3.34 ± 0.76 μg/ml after the second, to 4.11 ± 0.72 μg/ml following the third. The maximum concentrations of MEGX and GX were 0.66 ± 0.22 and 0.28 ± 0.08 μg/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 ± 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 ± 0.61 1/kg), and clearance divided by bioavailability (Cl/F, 11.65 ± 1.21 ml·kg−1·min−1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (±6 μg/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing. By considering the relative potencies of MEGX and GX to the parent drug and their concentrations attained, it is felt that MEGX, but not GX, may play an additive role in causing possible toxicity following epidural lidocaine. The authors recommend that the plasma concentration of lidocaine be monitored when the mean cumulative epidural dose of lidocaine HCl exceeds 900 mg.