UK-14, 304-18 (UK), a relatively selectiveα2- agonist, was examined for its effects on intraocular pressure (TOP) and pupil diameter (PD) in rabbits, cats and monkeys and on noradrenergic function in the cat nictitating membrane (CNM) preparation. Topical, unilateral administration of UK (0.0005-0.5 mg) produced dose-dependent decreases in IOP and pupil size in normal, unanesthetized rabbits, cats and monkeys. The ocular hypotensive effect of UK in the ipsilateral eye was delayed relative to the contralateral eye in all three species; UK produced an initial transient ocular hypertension in rabbits which was abolished by surgical transaction of three major extraocular muscles. Mean arterial blood pressure in rabbits was not affected by 0.005 mg UK topically. The ocular hypotensive and miotic effects of UK were attenuated in superior cervical ganglionectomized (SX) cats and rabbits. Intra-arterially administered UK (0.33, 1.0, 3.3 and 10µg) produced dose-related systemic hypotension and inhibition of contractions of the CNM elicited by electrically stimulating the pre-and postganglionic sympathetic trunks in the urethane/chloralose anesthetized cat. This inhibition was reversed and prevented by 300µg rauwolscine but not by 300µg domperidone. UK also enhanced the contractile response of the CNM to injected norepinephrine (10µg), UK suppressed ocular hypertension induced by water loading and IOP recovery rate following hypertonic saline infusion in rabbits suggesting that aqueous flow was inhibited. These results indicate that UK lowers IOP, in part, by suppressing sympathetic neuronal function which causes a reduction in aqueous flow.