The effects of the selective alpha2-adrenergic agonist p-aminoclonidine, the nonselective adrenergic agonist epinephrine, the selective beta2-adrenergic agonist fenoterol and the adenosine Ai agonist R-PLA on intraocular pressure were studied in control and pertussis toxin-pretreated rabbits. Pretreatment of rabbits with pertussis toxin decreased the ocular hypotensive effects of p-aminoclonidine and epinephrine, did not influence the same effects of fenoterol or R-PIA and markedly potentiated the initial ocular hypertensive effects of epinephrine and R-PIA. As far as the action on adenylyl cyclase in ciliary processes is concerned, isoproterenol stimulated its activity in control rabbits and epinephrine exerted dual, i.e. stimulatory and inhibitory effects on the activity of this enzyme. The data obtained with epinephrine and p-aminoclonidine confirm the view that their ocular hypotensive effects are associated with their inhibitory action on adenylyl cyclase and contradict the opinion that the hypotensive action of adrenergic drugs depends on adenylyl cyclase activation.