Release of ATP can be evoked from noradrenergic nerve varicosities isolated from guinea pig ileal myenteric plexus by depolarization with K+ and veratridine and during exposure to acetylcholine or 5-HT. Clonidine, however, modulates the release of [3H]noradrenaline without affecting the release of ATP. ATP is also released from noradrenergic sympathetic nerves in the vas deferens, where it mediates the initial depolarization and contraction in the smooth muscle. Factors that apparently modulate the release of noradrenaline do not produce corresponding effects on ATP release. The above results are best explained by the hypothesis that ATP and noradrenaline are stored in separate populations of vesicles within sympathetic nerves and that these pools are subject to differential presynaptic modulation. Depolarization of rat brain synaptosomes releases adenosine by a process that is mediated, at least in part, by efflux on the nucleoside transporter. Drugs that block the nucleoside transport (such as dipyridamole) reduce evoked adenosine release and may thereby diminish, rather than augment, the actions of adenosine at its receptors. Release of adenosine does not appear to be uniformly distributed throughout the brain insofar as release varies from synaptosomes prepared from different regions. Although the distribution of several markers for possible adenosine pathways in the brain, including adenosine release, do not show any consistent correlations, the non-uniform distribution for these markers suggests that adenosine may have differential functions in various brain regions.