Oral lidocaine analogues, such as tocainide, recently have been introduced to treat cardiac arrhythmias. The side effects of tocainide are similar to those of lidocaine, but possible interactions with lidocaine have not been examined thoroughly. With the increased use of these agents, emergency physicians must decide the safety of concurrent administration of lidocaine for local anesthesia or arrhythmia management. Twelve dogs were assigned randomly to either a lidocaine (L) or a tocainide/lidocaine (TL) group. The L group received lidocaine at a dosage of 0.5 mg/kg/min until the animals seized. The TL group received both loading and maintenance doses of tocainide to obtain therapeutic steady-state tocainide levels prior to receiving lidocaine at a dosage of 0.5 mg/kg/min. Venous blood samples to measure drug levels were obtained at 20-minute intervals and at the time of seizures. The average duration of lidocaine administration required to induce seizures in the L group was 70.0 +/- 7.5 minutes, and in the TL group 29.0 +/- 7.0 minutes (P less than .05). In addition, the average serum lidocaine level at the time of seizures was 11.2 +/- 1.0 micrograms/mL in the L group and 6.2 +/- 1.7 micrograms/mL in the TL group (P less than .05). Our results show that in animals the presence of a therapeutic serum level of tocainide lowers the seizure threshold following the administration of lidocaine. These findings may have important implications for clinical care because they suggest that lidocaine should be used cautiously and in reduced dosage in patients already taking tocainide.