A study has been made of the time courses of the pupillary and intraocular pressure responses of conscious rabbits to clonidine administered either topically or intravenously. Topical unilateral application of clonidine caused transient pupil dilatation and a biphasic intraocular pressure response; an initial hypertensive response preceded a hypotensive phase lasting several hours. Pupillary and hypertensive responses were absent in the untreated eye, but there was a rapid decrease of intraocular pressure. Intravenous administration of clonidine caused an immediate and large decrease of intraocular pressure in both eyes. Phenoxybenzamine given intravenously inhibited the pupillary dilatation and the hypertensive responses to clonidine. The role of efferent adrenergic neuronal activity in mediating the local biphasic pressure response was studied in rabbits with unilateral precervical and postcervical sympathotomy. The results showed the hypotensive response to be dependent on an intact adrenergic innervation of the ocular tissues.