The role of prejunctional purinoceptors (P 1-subtype) in the control of ATP-release from inhibitory motoneurons was investigated electrophysiologically, by studying fast purinergic inhibitory junction potentials (IJPs) in guinea-pig ileal circular muscle. Pressure ejections of adenosine and ATP (but not of α, β-methylene ATP) onto circular muscle depressed the amplitude of fast IJPs, indicating the presence of prejunctional P 1-purinoceptors. An adenosine (A 1/2)-receptor antagonist, theophylline (10 −8–10 −4 M), increased the amplitude of fast IJPs in a dose-related manner (EC 50 − 17.5 μM), suggesting the existence of a basal ‘adenosine tone’ that regulated ATP-release from ileal motoneurons. However, three methylxanthine derivatives, caffeine (10 −8–10 −4 M), 3-isobutyl-1-methylxanthine (IBMX; 10 −8–10 −4 M) and the potent A 1-receptor antagonist 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (DPCPX; 10 −8–10 −4 M), failed to potentiate fast IJPs and placed in doubt the existence of this inhibitory adenosine tone. Caffeine and IBMX, but not DCPCX, hyperpolarised ileal circular muscle in a dose-related manner and reduced IJP-amplitude; DPCPX did not alter the amplitude of IJPs. The non-specific inhibitor of phosphodiesterases, Ro-20-1724 (5 × 10 −7–5 × 10 −5 M), increased the amplitude of fast. IJPs, mimicking the actions of theophylline. To this extent, facilitation of inhibitory transmission appeared to involve phosphodiesterase inhibition and modification of intra-axonal cAMP levels and phosphorylation of intra-axonal protein kinases. The phenomenon of IJP rundown, presumed to be a manifestation of prejunctional autoinhibition, was studied using theophylline and DPCPX as A 1-receptor antagonists. Theophylline enhanced the extent of IJP rundown, while the more potent A 1-antagonist DPCPX was inactive, suggesting that IJP-rundown did not involve P 1/A 1-receptors. It was concluded that P 1-purinoceptors do not play a significant role in the regulation of evoked ATP-release, at least at low stimulus rates of less than 2 Hz, although P 1 purinoceptors were present on motoneurons. Instead, there appears to be another mechanism, regulated by intra-axonal phosphodiesterases and involving cAMP, that controls ATP-release from ileal motoneurons.