Nerves showing acetylcholinesterase (AChE) activity or immunoreactivity for substance P (SP) were demonstrated in the human cornea. AChE-positive fibres were found in stromal nerve trunks from where they penetrated Bowman's membrane and formed a basal epithelial plexus. Intraepithelial terminals arose from this network. SP immunoreactive nerve fibres showed similar architecture but were fewer. Both SP immunoreaction and histochemical AChE reaction were demonstrated consecutively in the same tissue section cut from both human and rabbit cornea. Stromal nerve trunks were found to contain SP immunoreactive and AChE-positive nerve fibres. However, the AChE-positive fibres were much more frequent than those immunoreactive for SP. In the rabbit Gasserian ganglion all neurons showed AChE activity but only some 20% were SP positive. It is concluded that all the sensory trigeminal nerve fibres of the cornea show AChE activity but only a proportion of them contain SP-like material.