MCP-1 and RANTES are molecules that regulate monocyte and T-lymphocyte recruitment towards sites of inflammation. We sought to evaluate the role of these chemokines in Alzheimer's disease (AD), and the effect of acetylcholinesterase inhibitor (AchEI) therapy on their release from peripheral blood mononuclear cells (PBMC). MCP-1 and RANTES mRNA expressions were determined by RT-PCR and the amount of secreted chemokines was assayed using specific ELISA methods from purified PBMC from each AD patients (n = 40) at the time of enrolment (T0) and after 1 month of treatment with AchEI (T1) and from 20 healthy age and sex-matched subjects (HC). We found that expression and production of MCP-1 in AD patients was significantly lower than in HC subjects. After 1 month of therapy with AchEI (Donepezil), MCP-1 levels increased in each patient. However, higher levels were detected for RANTES in AD patients compared to control subjects and in AD patients treated with Donepezil. MCP-1 and RANTES have a compensatory role in balancing the impaired mechanisms involved in immune response during ageing. Our present findings suggest that these two chemokines are both involved in AD pathogenesis and might reflect different states of activation and/or responsiveness of PBMC from AD patients, contributing to the impaired of the peripheral immune system in these patients.