Nerve excitability is principally determined by the state of membrane sodium channels, which can be influenced by factors such as drugs or the ionic composition of the extracellular fluids. The excitability of isolated nerves is increased by lowered extracellular calcium and hydrogen ion concentrations, and similar effects are seen on intradental nerve excitability. This is of interest as some agents used to desensitize hypersensitive dentine are believed to act by reducing intradental nerve excitability. A variety of ions, including potassium and divalent cations, have been shown to reduce intradental nerve excitability when applied in relatively high concentrations to dentine close to the pulp. However, these conditions do not mimic the clinical situation, where agents are applied to outer dentine, up to 2 mm from the pulp. Also, when agents are applied to dentine it is difficult to quantify the precise changes in extracellular fluid composition, and there is the additional complication of possible interactions between the agents and dentine. These problems can be minimized by using isolated nerves, which allow better control over the conditions and ionic concentrations necessary to achieve nerve conduction block. Such methods can provide a convenient way to screen potential desensitizing agents before evaluation in vivo or in clinical trials.