Inflammation has been involved in the pathogenesis of dementia. The study evaluates the presence and the source of pro- and anti- inflammatory cytokines in the blood of patients with Alzheimer's disease (AD), multi-infarct dementia (MID) or in non-demented elderly people (controls). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor I (sTNF-RI) plasma concentrations and release from blood cells stimulated with lipopolysaccharide (LPS, 1 microg/ml) were determined. The results show that TNF-alpha released from blood cells is significantly decreased (27%) in all demented patients compared to controls. Circulating TNF-alpha is increased (400%) only in MID patients. In these patients plasma levels of sTNF-RI are increased (53%) and IL-10 from stimulated blood cells decreased (47%) compared to non-demented subjects. The results show that: (1) peripheral production of TNF-alpha is blunted in demented (both AD and MID) patients compared to non-demented age-matched subjects; (2) AD patients have a selective disregulation of the peripheral TNF-alpha system; (3) different cytokines are up- or down- regulated in MID patients showing that in this condition the pro- and anti-inflammatory peripheral cytokine system is more widely affected.