In 12 healthy volunteers, the effects of a single oral dose of nimodipine (40 mg) on pupil size and on the mydriasis induced by conjunctival instillation of tyramine and phenylephrine were studied by using a TV monocular infrared pupillometer. Nimodipine alone was unable to modify the pupil area. When compared with placebo, the Ca2+ entry blocker reduced the pupil dilation caused by tyramine, whereas it did not affect the phenylephrine-induced mydriasis. Since tyramine provokes mydriasis by releasing neuronal norepinephrine, a full adrenoceptor agonist, whereas phenylephrine acts only on alpha 1-adrenoceptors insensitive of extracellular Ca2+, the hypothesis may be advanced that a heterogeneous population of alpha-adrenoceptors, located in the human iris dilator muscle and differently sensitive to Ca2+ entry blockade, is responsible for the reduction of the tyramine-induced mydriasis. Apart from this putative mechanism, the results suggest that nimodipine reduces the pupillary response to adrenergic activation in the human eye.