Hydra (Cnidaria) is the first animal organism to have developed a neural network, which has been proposed to control, inter alia, the f eeding response , i.e. a mechanism through which the coelenterate opens and then closes its mouth in the presence of prey and/or glutathione. Here, we report that Hydra contains: (i) selective cannabinoid binding sites; (ii) the endogenous cannabinoid receptor ligand, anandamide (arachidonoylethanolamide); (iii) a fatty acid amide hydrolase-like activity catalysing anandamide hydrolysis; and (iv) the putative biosynthetic precursor of anandamide, N-arachidonoylphosphatidylethanolamine. We suggest that this e ndogenous cannabinoid system is involved in the modulation of the f eeding response . Anandamide (1nM-1μM) potently inhibited (up to 45%) the glutathione-induced f eeding response by accelerating Hydra vulgaris mouth closure. The effect was maximal at 100nM anandamide and was reversed by the selective antagonist of the CB 1 subtype of mammalian cannabinoid receptors, SR 141716A (50-100nM). Specific cannabinoid binding sites were detected in membranes from Hydra polyps by using [ 3 H]SR 141716A (K d =1.87nM, B m a x =26.7fmol/mg protein), and increasing anandamide concentrations were found to displace the binding of [ 3 H]SR 141716A to these membranes (K i =505nM). Hydra polyps were also found to contain amounts of anandamide (15.6pmol/g) and N-arachidonoylphosphatidylethanolamine (32.4pmol/g), as well as the other e ndocannabinoid 2-arachidonoylglycerol (11.2nmol/g), comparable to those described previously for mammalian brain. Finally, a fatty acid amide hydrolase activity (V m a x =3.4nmol/min/mg protein), with subcellular distribution, pH dependency and sensitivity to inhibitors similar to those reported for the mammalian enzyme, but with a lower affinity for anandamide (K m =400μM), was also detected in Hydra polyps.These data suggest that the endocannabinoid signalling system plays a physiological role in Hydra that is to control the feeding response. Hydra is the simplest living organism described so far to use this recently discovered regulatory system.