BACKGROUND: The failure to achieve satisfactory anesthesia following the administration of local anesthetic agents in acute inflammatory tissues is a recognized clinical phenomenon. Many inflammatory mediators can reduce the threshold of nociception during inflammation, and histamine, one of the most important inflammatory mediator, may attenuated local anesthetic effect during inflammation. The purpose of this study was to investigate if histamine can antagonize a lidocaine induced nerve block in vitro. METHODS: Recordings of the compound action potentials (CAP) of A-fiber components were obtained from the isolated sciatic nerves of male Sprague-Dawley rats. The nerve sheath of the sciatic nerve was removed and desheathed nerve was mounted in a recording chamber. Single pulse stimuli (0.5 msec, supramaximal stimuli) were repeatedly applied (2 Hz) to one end of the nerve and CAP recordings were made at the other. The effect of histamine on the suppression of CAP by lidocaine and the effect of histamine on the recovery time to the nerve block by lidocaine were measured. RESULTS: Compared with the baseline amplitude, the amplitudes of CAP were 11.7+/-4.1% for the lidocaine group, 18.3+/-4.6% for the lidocaine histamine 0.05% group, and 26.1+/-5.6% for the lidocaine histamine 0.5% group. Nerve block recovery times were: 38.6+/-3.5 min for the modified Krebs group, 29.8+/-4.2 min for histamine 0.05% in the modified Krebs group, and 19.2+/-1.1 min for histamine 0.5% in the modified Krebs group. CONCLUSIONS: Histamine shortened the recovery time induced by lidocaine. We suggest that histamine may significantly attenuate the effects of local anesthetics in inflammed tissue.