No information is yet available on the effect of tumor necrosis factor alpha (TNFalpha) on amyloid beta protein (Abeta)-induced cytotoxicity in human cells. For this reason the induction of apoptosis by TNFalpha and Abeta (25-35) was studied in primary cultures of human thyroid and kidney cells as well as in the neuroblastoma line SK-N-SH and in DU-145 cells. Apoptosis occurred in all cell types after Abeta (25-35) treatment, but was markedly enhanced when TNFalpha was additionally present. This effect was less pronounced in transformed cell lines than in primary cultures, in which TNFalpha on its own was not cytotoxic. Apoptosis was still more prevalent under serum free culture conditions. The results demonstrate that TNFalpha may support the occurrence of Abeta-mediated cell death and thus contribute to the development of pathological changes in Alzheimer's disease (AD).