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A characteristic feature of neuritic plaques in Alzheimer''s disease is represented by the presence of activated astrocytes, surrounding dystrophic neurons and β-amyloid deposition. To explore the role of astrocytes in in vitro β-amyloid neurotoxicity, we studied the effect of β-amyloid treatment in hippocampal neurons in two different cell models: pure cultures, where neurons were grown in absence of astrocytes and mixed cultures, where neurons were seeded on a confluent layer of astrocytes. We evaluated two characteristic aspects of in vitro β-amyloid neurotoxicity: reduction of cell viability and degeneration of the neuritic tree. We demonstrated that neurons growing on astrocytes were more prone to the detrimental effect of the amyloid peptide, with respect to neurons grown in absence of the glial component. Our results support the hypothesis that β-amyloid–astrocyte interaction can adversely condition neurons and contribute to neuronal damage in Alzheimer''s disease. [Copyright &y& Elsevier]