An overview of the ocular hypotensive actions of some α2-agonists with imidazoline structures is presented. These agents inhibit isoproterenol-stimulated adenylate cyclase (AC) activity in ciliary process membrane through a Na+ and GTP-dependent mechanism. Receptor binding studies with the α2-agonist radioligand [125I] p-iodoclonidine ([125I]PIC) in rabbit ciliary body membranes indicate that the α2-receptor subtype is α2A. Gpp(NH)p and NaCl dose-dependently decreased the number of [125I]PIC binding sites by shifting the receptor-G protein complexs from the high affinity state to the low affinity state for agonist binding. This is consistent with the observations that inhibition of AC was Na+ and GTP dependent. The NaCl and Gpp(NH)p effects on binding appeared to be through different mechanisms. The α2-receptor in ciliary process thus appears to be an α2A-receptor that is negatively coupled to the AC-cAMP generating system.