The ability of the extracellular nucleoside adenosine to regulate metabolism has been intensively studied since the original description of the cardiovascular effects of adenosine administration made by Drury and Szent-Gyorgyi (1929). Subsequent studies over the next four decades uncovered a vast array of effects of purinergic compounds on many different cell types and prompted the adoption of what is presently the basis of the currently accepted nomenclature for purinergic receptors (Burnstock, 1978). As described by Burnstock, receptors were classified in accordance with their preference for binding either adenosine (P, receptor subtypes) or adenine nucleotides (P,, subtypes). P, receptors were further distinguished from P, receptors by the sensitivity of their effects to inhibition by alkylxanthine compounds, such as caffeine or theophylline (Burnstock, 1978). P, receptors were initially divided into A, and A, subtypes based on their a’bility to inhibit and stimulate CAMP accumulation respectively (Burnstock, 1978). The subsequent development of subtype-selective agonist and antagonist ligands facilitated the identification of A, and A, adenosine receptor (AR) proteins via photoaffinity labelling (reviewed in Stiles, 1990). Importantly, the development of high affinit. y, selective A, AR antagonists facilitated the purification of the receptor from several sources (Jacobson et al., 1985; Nakata, 1989; Olah et al., 1990; Freissmuth et al., 1991a) and allowed its reconstitution with inhibitory G-proteins (see below). Undoubtedly, the molecular cloning of multiple CD-NAs encoding various AR subtypes has ushered in a new era in AR research. The ablility to express both wild type and mutated recombinant ARs has already led to significant increases in the understanding of the molecular interactions involved in ligand binding as well as the molecular nature of various modes of regulation of receptor function. In this review, we will describe the basic properties of the various cloned AR subtypes and how these relate to the ARs expressed endogenously. Finally, we will describe how expression of recombinant