Using high-performance liquid chromatography, gaschromatography and chromato-mass spectrometry methods a novel endogenous cyclic dipeptide cyclo-prolylglycine was identified in rat brain. Its content according to gas chromatography is 2.8 + 0.3 nmol/g wet brain. Synthetic cyclo-prolylglycine has demonstrated antiamnesic activity in the passive avoidance test in rats at a dose of 0.1 mg/kg i.p. Cyclic dipeptide cyclo-prolylglycine seems to be a memory facilitating substance and its presence in rat brain suggests the existence of a new mechanism of memory regulation.Key words: Cyclo-prolylglycine; Endogenous cyclic dipeptide; Memory facilitating substance displays activity due to interaction with one vasopressin receptor subtype. We have found out, however, that unlike piracetam, which facilitates the initial processing of memory engram as well as consolidation, the dipeptide pGlu-Asn-NH2 improved only the phase of information input and retrieval, but did not influence consolidation [10]. On the other hand, proline-containing dipeptide analogues of piracetam facilitated consolidation [11]. The cyclic dipeptide cyclo-(Pro-Gly) turned out to be the most active of them [12]. This cyclic dipeptide can be assumed to be one of the endogenous ligands of hypothetic 'nootropic receptors', which selectively regulates the processes of training and memory. This work is devoted to the identification of endogenous cyclo-(Pro-Gly) in rat brain.