In order to examine the clinical usefulness of
methacholine in assessing the site of ocular parasympathetic lesions, pupillary responses in man were measured in postganglionic (
Adie's syndrome) and preganglionic third nerve lesions involving the pupil and in controls. From previous work with
methacholine it might have been expected that greater constriction would occur in the postganglionic lesions but similar responses were found in both. Corneal
hypoxia due to ptosis appeared unlikely to affect corneal permeability significantly and it is probable that these results reflect an increase responsiveness of the iris at, or distal to, the site of
muscarinic acetylcholine receptors. Pupils contralateral to
third nerve palsy, when tested on a separate occasion, also constricted by an amount approximately proportional to that of the clinically abnormal pupil. The possibilities that this may result in some way from reduction in total
retinal illumination, or from retrograde changes in preganglionic pupilloconstrictor neurons affecting contralateral pupilloconstrictor neurons via central pathways, are discussed. It is concluded that supersensitivity to
methacholine, tested carefully in the manner described, is a useful guide to the presence of
parasympathetic denervation or decentralization, but that it is not reliable in distinguishing between the two sites.