A gas-liquid chromatographic method for the simultaneous measurement in serum of bupivacaine, lidocaine, and their main metabolites, 2,6-pipecolylxylidide (PPX) and monoethylglycine xylidide (MEGX), respectively, is described. The procedure involves a one-step extraction and injection of the extract into a gas chromatograph equipped with a capillary column and nitrogen phosphorus detector under constant temperature conditions. Recovery of all components averaged 94%, with the lowest detection limit of 15 ng/ml for the four drugs. The precision within-series coefficients of variation ranged from 7.7% for bupivacaine, 8.6% for lidocaine, 10.2% for MEGX, and 15.8% for PPX. The interday coefficients ranged from 0.7 to 6.5%. Concomitant use of caffeine and carbamazepine may interfere with MEGX and bupivacaine determination, respectively. For this reason, in patients receiving one of these two drugs (or ingesting foods and beverages containing caffeine), the described method is not recommended.