In this review, Joel Linden summarizes what is known about a new and intriguing member of the adenosine receptor family, the A3 receptor. This receptor exhibits unusually large differences in structure, tissue distribution and pharmacological properties between species. Rat A3 receptors are resistant to blockade by xanthine antagonists, but human and sheep A3 receptors can be potently blocked by certain xanthines, notably acidic 8-phenylxanthines. One function of the receptor is to facilitate degranulation of mast cells, and a role for mast cells and A3 receptors in mediating myocardial preconditioning has been proposed. Therefore, selective antagonists of A3 receptors have potential for the treatment of allergic, inflammatory and possibly ischaemic disorders.