In man, stimulation of nerves in teeth causes pain, and there is little evidence that these afferents contribute to any other sensation. The enamel that covers the crown of a tooth is non-vital and insensitive, but thermal stimulation of the enamel is capable of evoking pain by exciting sensory receptors in the underlying dentine or dental pulp. By contrast, dentine may be very sensitive; so much so that even very gentle stroking of an exposed dentine surface with a wisp of cotton wool may cause pain. Other forms of stimulus that may cause pain from exposed dentine include thermal, mechanical, changes in hydrostatic pressure, solutions of high osmotic pressure and drying. The dentine is sensitive throughout its thickness. Dental pulp is even more sensitive and, if it should become exposed by injury or dental caries, is usually extremely painful. For this reason, little is known of its sensitivity to different stimuli. Information about the innervation of the dentine and pulp has come mainly from studies on anaesthetised cats and rats. Dental pulp is densely innervated by the terminals of Aβ, Aδ and C-fibres, and some of these terminals extend up to ca 100 µm into the tubules that traverse the dentine. These terminals are very fine (diameter ca 0.1 µm) and non-myelinated. Not all tubules contain nerves but each contains the process of an odontoblast cell, although this process does not extend more than about half the length of the tubule. The outer ends of the tubules appear to contain no vital cellular material and little other than extracellular fluid. In the cat canine tooth the dentine is about 2 mm thick. Electrophysiological studies show that there are broadly two classes of intradental afferent: a group of Aβ and Aδ fibres that respond to any of the stimuli that will cause pain in man, and a group of slower conducting Aδ and C-fibres that respond mainly to heating of the tooth but also to chemical stimuli such as bradykinin when they are applied to exposed pulp. The first group appears to share a common transduction mechanism that involves displacement of the contents of the dentinal tubules (the hydrodynamic mechanism) in which the tubules provide hydraulic links between the exposed dentine surface and the nerve terminals in the inner dentine or the pulp. All the stimuli that excite these nerves produce flow in the dentinal tubules and the afferents have been shown to be more sensitive to outward than inward flow. The receptor appears therefore to be some form of mechanoreceptor, although the flow may cause cell damage with resultant local chemical changes that stimulate nociceptors. The effects of drugs on the function of the nerve terminals can be studied by applying the drugs under pressure to exposed dentine, although it is difficult to estimate the concentration achieved at the site of action. Local anaesthetics applied in this way block the sensory responses, and preliminary experiments indicate that the responses can also be attenuated by calcium channel blockers such as nickel, but substances known to block stretch-sensitive ion channels such as gadolinium and amiloride have no specific effects. Neither ATP nor capsaicin excite these receptors. The second group of heat-sensitive afferents appears to be more deeply located in the pulp and they respond to topical applications of capsaicin. There is some evidence for purinergic (P2X3) receptors but no evidence of VR1 receptors in dental pulp.