The purpose of this review is to analyse critically our present knowledge on purine release, and in particular the role of these substances as modulators of the nervous transmission. Multiple purine receptor subtypes have been identified, cloned and functionally characterised. Neurons and glial cells are considered to be important sources of extracellular adenine-based purines. The released nucleotides and nucleosides, by interacting with their specific neuronal and glial receptors, activate a complex autocrine and/or paracrine system for the modulation of the release either of neurotransmitters or the purine ones. Guanine-based purines which are released from astrocytes co-operate with adenine-based compounds in this modulation.