In baboons, lidocaine HCl was injected into the lingual (3 mg/kg), brachial (7 mg/kg), or femoral (7 mg/kg) arteries. Blood samples were taken from the internal carotid artery (ICA), internal jugular (IJV), external jugular (EJV), brachial (BV), or femoral (FV) vein, depending on the injection site, 6, 30, and 180 seconds after injection. Subsequently, radioactive microspheres (20, μ in diameter) were injected into the lingual artery, and the brains were obtained 48 hours later at postmortem to locate the microspheres. Six seconds after injection into the lingual artery, lidocaine concentration in ICA was 28 μg/ml, whereas peak levels in IJV and EJV occurred at 30 seconds, being 51 and 25.7 μg/ml, respectively. After injection into the brachial artery, peak average ICA levels were 105.5 μg/ml at 6 seconds, while only 20.6 μg/ml concentration was noted in ICA after injection into the femoral artery. Seventy-four percent of the Sr90 labeled micro-spheres were found lodged in the ipsilateral cerebral hemisphere. Local anesthetic drugs accidentally injected into arteries may reach the cerebral circulation following a centripetal pathway and thus produce central nervous system toxic responses.