Growing evidence indicates that amyloid (Aβ) deposition and phagocyte activation participate in inflammatory reactions in the brain during the course of Alzheimer's disease. To further investigate the effects of Aβ-phagocyte interaction, we examined the production of proinflammatory (IL-1β, IL-6), chemotactic (MIP-1α, IP-10) and inhibitory (IL-1Ra, IL-10 and TGFβ 1 ) cytokines by cultured human monocytes and mouse microglial cells upon stimulation with Aβ[25-35]. Northern blot analysis and specific immunoassays demonstrated that Aβ[25-35] triggers mRNA expression and release of IL-1β, IL-1Ra and MIP-1αbut not of IL-6, IL-10, TGFβ 1 and IP-10 from human monocytes. Similar results were obtained by examining the production of IL-1β, IL-6 and IL-10 from mouse microglial cells in the same experimental conditions. Taken together, these data indicate that Aβ-phagocyte interaction can drive a different response towards cytokine production by monocytes and microglia, with a particular proinflammatory trend, and further support a role for Aβ deposition as a triggering factor of inflammatory events in Alzheimer's disease