A standardized method of testing irideal sensitivity to 1% phenylephrine and 0.05% pilocarpine is described, and a quantitative basis for pupillary neurotransmitter "supersensitivity" established. In a normal 20-year-old subject the pupillary diameter increases in bright light by no more than 2.1 mm 1 h after ocular application of phenylephrine; this figure should be adjusted for age since "phenylephrine sensitivity" of the iris increases by 0.23 mm per decade. The pupillary diameter, when measured in darkness, has normally decreased by less than or equal to 1.4 mm within 30 min of administration of pilocarpine. Differences in drug-induced diameter alterations between pairs of pupils should not normally exceed 0.7 mm for phenylephrine or 0.4 mm for pilocarpine. Seventy one percent of sympathetically denervated or decentralized (Horner's) pupils and 41% of parasympathetically denervated ("tonic") pupils are abnormally responsive or "supersensitive" to dilute solutions of phenylephrine and pilocarpine respectively. Supersensitivity to these agents is therefore a useful but not invariable diagnostic feature of disturbed irideal innervation.