Changes in intraocular pressure and pupil diameter were studied in rabbits following topical administration of relatively selective and non-selective adrenergic agonists. Drugs having strong α-adrenoceptor stimulating effects (norepinephrine, phenylephrine, epinephrine) initially produced a transient increase in intraocular pressure and pupil diameter before eliciting any ocular hypotensive effects. In contrast, those drugs with predominately β-adrenoceptor stimulating properties (isoproterenol, isoetharine, metaproterenol, terbutaline, salbutamol, carbuterol) produced an immediate decrease in intraocular pressure without causing ocular hypertension or mydriasis. Significantly, the decreases in intraocular pressure were more pronounced with those drugs having strong β 2-adrenoceptor stimulating activity. Thus, stimulation of α- and β-adrenoceptors can produce opposite initial effects on intraocular pressure, but α-adrenergic mechanisms may interact with β 1- and/or β 2-adrenoceptor mechanisms to produce subsequent ocular hypotension. Most importantly these data indicate that more selective β 2-adrenoceptor stimulation is an effective mechanism for lowering intraocular pressure.