The IOP and pupil response to alpha-adrenergic agonists and blockers was studied in albino rabbits. Topical ocular application of solutions of methoxamine (alpha 1) and oxymetazoline (alpha 2) caused dose-related early rises in IOP which were inhibited by pretreatment with prazosin, an alpha 1-blocker, or with yohimbine, an alpha 2-blocker. Although both prazosin and yohimbine have ocular hypotensive activity, the effect on the early IOP rise did not appear to be related to this action. Prazosin and yohimbine also inhibited the early IOP rise after treatment with clonidine, a second alpha 2-agonist. Surgically sympathectomized rabbits showed little or no hypersensitivity to methoxamine or oxymetazoline when compared to non-operated normal rabbits. However the treated ipsilateral eyes showed a much greater increase in IOP than the treated contralateral eyes. There was little difference in the IOP response between clonidine-treated ipsilateral and contralateral eyes. Methoxamine and oxymetazoline caused dose-related increases in the pupil diameter which were blocked by the nonselective alpha-blocker phentolamine but not by prazosin (alpha 1) or yohimbine (alpha 2). This study suggests: 1) That the early IOP rise after treatment with alpha-agonists is due to stimulation of postsynaptic alpha 1-receptors, possibly located in superficial blood vessels in the anterior segment of the eye; 2) The mydriatic response to alpha-agonists appears to be mediated by alpha-receptors which differ from the classical alpha 1 and alpha 2 subtypes.