Introduction. Idiopathic normal-pressure hydrocephalus (iNPH) is a neurological disease that develops in elderly. It has been hypotized that cerebrovascular disease could have a role in etiolology of hydrocephalus. Evidences show a possible alteration of immune system in iNPH patients. Adenosine (Ado) is a metabolite produced in response to ischemia, hypoxia, inflammation and trauma. The effects of Ado are transduced through four subtypes of receptors: A1 (A1R), A2A (A2AR), A2B and A3. Aim. The aim is to evaluate expression of A1R and A2AR in peripheral blood mononuclear cells (PBMCs) from iNPH compared to control subjects (CT). We investigate if Ado system, that plays an important role in CNS, in vascular system, and in inflammation, is involved in pathophysiology of iNPH. Results. We analysed 22 iNPH and 50 CT age and gender-matched. Data showed that A1R mRNA levels in PBMCs from iNPH were significantly lower than CT (0.84±0.12 and 2.42±0.42, respectively; p=0.001) as well as A1R density (0.31±0.02 and 0.42±0.04; p=0.043). A2AR gene expression was significantly lower in iNPH than CT (0.65±0.09 and 1.5±0.14; p<0.001). Conclusions. Since PBMCs may provide a window into the CNS, we could speculate that there is a down-regulation of these receptors also in the CNS. Since Ado receptors control the dynamics of brain vasculature and of inflammation, we could assume that the down-regulation of A1R and A2AR may have a key role in iNPH. Our findings underline the role of Ado system in iNPH as peripheral marker of this disease with unknown pathophysiology.