Lactate dehydrogenase (LDH) enzyme activity was measured in the supernatant of rat aortic endothelial cell cultures to evaluate the cytotoxic effects of two proinflammatory mediators such as LPS and histamine, as well as beta-amyloid protein (fragment 1-28) on endothelial cells. In the same culture we also studied the influence of different sera from patients with Alzheimer's disease (AD) or healthy elderly subjects. The results indicate that very low concentrations (1 microgram/ml) of beta-amyloid or histamine (1 microM) were able to produce cell damage after an incubation time of 4 h. Treatment with LPS induced cell damage at the highest concentration (2.5 micrograms/ml) after 24 h of incubation. When endothelial cells were treated with serum from AD and non-AD individuals, an inhibition of endothelial cell proliferation was observed only with activated AD serum. These results indicate that rat endothelial cell cultures represent an important model to study inflammatory mediators and to evaluate the therapeutic effect of antiinflammatory molecules in AD and other neurodegenerative disorders.