The effects of 3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)-1-propylxanthine (I-ABOPX; BW-A522), which has nanomolar affinity for the recently cloned human and sheep adenosine A3 receptor, on the putative A3 receptor mediated hypotensive response to N6-2-(4-aminophenyl)ethyl adenosine (APNEA) in the rat have been investigated. Following blockade of A1 and A2 receptors with 8-(p-sulphophenyl)theophylline, BW-A522, 10 and 40 mg/kg i.v., blocked dose-dependently and surmountable the hypotensive response to APNEA. The results provide direct evidence of an A3 receptor in the cardiovascular system of the rat which induces hypotension when activated.