CONTEXT: Contrasting findings have been published regarding the role of magnesium sulphate used as an additive to local anaesthetics in peripheral nerve blocks. OBJECTIVE: To clarify the effect of magnesium sulphate on nerve excitability. SETTING: C and Aβ compound action potentials were recorded extracellularly in vitro in saphenous nerves from adult rats. ANIMALS: Saphenous nerves (n = 30) from male Wistar rats (n = 19), 12 to 16 weeks old. INTERVENTION: Primary sensory afferents were tested with a computerised threshold tracking program (QTRAC) with a supramaximal 1 ms current pulse either alone or after 300 ms of conditioning polarising ramp currents in the presence and absence of 10 mmol l magnesium sulphate, 80 μmol l lidocaine and a combination of both. MAIN OUTCOME MEASURES: Changes in current thresholds to elicit compound action potential amplitudes of 40% of the maximal response. RESULTS: Magnesium sulphate increased excitability thresholds to a greater extent in Aβ fibres than in C fibres. It enhanced the effects of lidocaine in both Aβ fibres [mixture 0.470 mA (SD 0.105) versus lidocaine 0.358 mA (SD 0.080), P < 0.001] and C fibres [mixture 2.531 mA (SD 0.752) versus lidocaine 2.385 mA (SD 0.656), P = 0.008]. Preconditioning experiments also showed that magnesium sulphate had an enhancing effect with lidocaine in Aβ fibres [mixture 0.620 mA (SD 0.281) versus lidocaine 0.543 mA (SD 0.315), P = 0.005], but not in C fibres [mixture 2.412 mA (SD 0.641), lidocaine 2.461 mA (SD 0.693), P = 0.17]. CONCLUSION: These results suggest that the binding of magnesium ions depends on both the type and conformational state of voltage-gated sodium channels. They also may help to explain the conflicting reports regarding the clinical effects of magnesium sulphate as an additive to lidocaine in peripheral nerve blocks.