Whereas the traditional view of humoral control of renal function by circulating hormones is well established, the concept of an ‘intracrine’ system, that is, additional regulation by an intrinsic system of locally produced autocrine or paracrine factors, has emerged only recently. Putative, though in most cases ill-defined, intrarenal systems include locally generated angiotensin II, endothelins, eicosanoids, nitric oxide (NO), some growth factors and even proteases that can activate receptors or transport proteins. Extracellular nucleotides (ATP, ADP, etc.), their receptors (P2 receptors), and their degradative enzymes make up another complex, though in some ways better-defined, system. Although known to fulfil a variety of functions elsewhere in the body, it is only in the last decade that the renal effects of extracellular nucleotides have received more attention. Two classes of P2 receptors exist: ligand-gated cation channels (P2X receptors, subtypes P2X1-7) and G protein-coupled P2Y receptors (subtypes P2Y1, 2, 4, 6 and 11-14). A range of P2 receptors from both classes has been identified in the glomerulus and renal tubule, on both apical and basolateral membranes; there is also evidence that ATP is secreted by the renal tubule in high enough concentrations to stimulate P2 receptors. What is more, the enzymes that can degrade secreted nucleotides (ectonucleotidases) are present throughout the nephron. In vivo and in vitro studies have demonstrated a diversity of nucleotide effects: activation of apical P2Y1 receptors in the proximal tubule inhibits bicarbonate reabsorption (via NHE3); in vitro studies suggest that P2 receptor activation also inhibits proximal tubular phosphate reabsorption; yet glucose uptake and gluconeogenesis are both stimulated. There are no in vivo data for the loop of Henle, but in vitro experiments have shown that stimulation of P2Y2 receptors and/or an unidentified P2X receptor inhibit Na+-K+-2Cl- co-transport in the thick ascending limb, involving NO release. In the collecting duct, P2 receptor activation (apical and/or basolateral) has been shown to inhibit K+ channel activity, vasopressin-stimulated water reabsorption, and ENaC-mediated sodium reabsorption. While still not completely resolved, pharmacological profiling and experiments in transgenic mice suggest that P2Y2 is the receptor subtype responsible for these effects, although there seem to be important species differences in P2 receptor distribution and function – yet another feature of this system that has to be considered. Finally, P2-mediated actions may have a significant pathophysiological role, particularly in renal parenchymal and vascular injury (P2X7), and in renal cyst formation (P2Y2 and/or P2X7). However, there is still much to understand about the physiological/pathophysiological role(s) of this primitive and fascinating autocrine/paracrine system, and it is likely to provide a novel therapeutic target in the future.