Adenine nucleosides and nucleotides have multiple effects as extracellular mediators in every organ system and initiate or modulate cellular responses via cell surface receptors. Current evidence indicates the existence of four receptors for adenosine: A1, A2A, A2B, and A3. These G protein-coupled receptors transduce activation or inhibition of adenylate cyclase and phospholipase C. Reasonably selective antagonists are available for some adenosine receptor subtypes. The receptors for adenine nucleotides, such as adenosine triphosphate (ATP), now encompass seven distinct P2X class receptors (P2X1 through P2X7) and ten P2Y subfamily receptors: P2Y1 through P2Y11 (the former P2Y7-receptor is no longer included as a subtype). Five of these receptors are mammalian. Despite its structure, uridine triphosphate (UTP) is a potent ligand at several P2Y-receptors. Responses to P2X-receptor stimulation result from activation of nonselective cation channels in the cell membrane. P2Y-receptor activation stimulates signaling mediated via phospholipase C. There is a paucity of specific antagonists for P2X- and P2Y-receptors, and their characteristics have been defined through the use of relative agonist potencies. Additional information about the molecular characteristics of these receptors, their pharmacologic properties, and associated signaling pathways can be found in several recent compendia and reviews.