In the present study the imidazoline radioligand 3H-RX 781094 (idazoxan) was used to characterize the α2-adrenergic receptors in basolateral membranes of rabbit proximal tubule. Scatchard analysis of equilibrium binding data showed that 3H-RX 781094 labels 566 ± 118 fmol/mg protein of binding sites with an apparent dissociation constant (K) of 1.45 ± 0.14 nmol/l. However, in competition studies, only 25% of the 3H-RX 781094 binding was inhibited by catecholamines and α2-adrenergic compounds; the remaining 75% of specific binding was inhibited only by molecules having an imidazoline or oxazoline ring with the following order of potency: cirazoline > tolazoline > UK 14 304 > rilmenidine > clonidine. These data suggest that imidazoline compounds bind to both α2-adrenergic receptors and to a `non-adrenergic site' which might be defined as an imidazoline-preferring receptor. Based on these results, it is possible to hypothesize that imidazoline and oxazoline drugs, such as clonidine and rilmenidine, exert their hypotensive activity partly through the stimulation of imidazoline receptors.