Intravenous lidocaine has been shown to relieve acute postoperative pain and chronic neuropathic pain. It is not known whether analgesia produced by 2-10 micrograms/ml plasma concentrations of lidocaine is due to an effect on peripheral-pain-transducing nerves or to central nervous system effects. The current study examined effects of analgesic concentrations of lidocaine on injury-induced discharge of A-delta and C fibers, using the in vitro rabbit corneal nerve preparation. Lidocaine at concentrations from 1-20 micrograms/ml reversibly suppressed tonic action potential discharge of acutely injured nerves. The median effective concentration (ED50) (5.7 micrograms/ml) corresponds to clinically effective plasma concentrations for analgesia. Electrically evoked nerve conduction was not blocked until lidocaine concentrations were greater than 250 micrograms/ml. Thus, analgesia produced by lidocaine appears to result from suppression of tonic neural discharge in injured peripheral A-delta and C fiber nociceptors.