Alterations in arterial PaCO 2 can influence local anesthetic toxicity. The objective of this study was to evaluate the effect of stress-induced changes in PaCO 2 and PaO 2 on the seizure threshold of lidocaine and articaine. Lidocaine (2% with 1 : 100,000 epinephrine) or articaine (4% with 1 : 100,000 epinephrine) was administered intravenously under rest or stress conditions to 36 rats separated into 4 groups. Propranolol and prazosin were administered preoperatively to minimize cardiovascular effects of epinephrine. Mean arterial pressure ( MAP ), heart rate ( HR ), and arterial pH, PaCO 2 , and PaO 2 were measured. Results showed no differences in MAP, HR, or pH. Stress significantly increased the latency period for the first tonic-clonic seizure induced by a toxic dose of both lidocaine and articaine (P , .05). Seizures were brought on more rapidly by articaine. No significant difference between toxic doses of lidocaine and articaine was noted. Stress raised the seizure threshold dose for both drugs and significantly (P , .01) increased arterial PaO 2 from 94.0 6 1.90 mm Hg to 113.0 6 2.20 mm Hg, and reduced PaCO 2 from 36.0 6 0.77 mm Hg to 27.0 6 0.98 mm Hg. In conclusion, reduction in PaCO 2 and/or increase in PaO 2 raised the seizure threshold of lidocaine and articaine. This study also confirmed that lidocaine and articaine have equipotent central nervous system toxicity.