The role of neuronal injury and glial inflammatory responses in Aizheimer's disease has been highlighted by recent epidemiological work establishing head trauma as an important risk factor and by the use of anti-inflammatory agents as an important ameliorating factor in this disease. Our studies have advanced the hypothesis that chronic activation of glial inflammatory processes is engendered by genetic or environmental insults to neurons, via neuronal signaling of microglia to become activated and to excessively elaborate the pro-inflammatory cytokine interleukin-1. This step sets in motion an interleukin-1 driven cytokine cycle of cellular and molecular events that is at once attractive in the short term, because of potential neuronotrophic consequences, and harmful in the long term, because of chronic neurodegenerative consequences. In this cycle, interleukin-1 1) promotes excessive synthesis and processing of the beta-amyloyd precursor protein and other beta-amyloid plaque-associated proteins and 2) activates astrocytes with promotion of astrocytic synthesis and release of a number of inflammatory and neuroactive molecules. One of these interleukin-1-regulated astrocyte-derived molecules, S100Beta, is neuronotrophic. However, S100Beta may stress neurons, perhaps old ones in particular, as it promotes neurite growth and, like interleukin-1, induces excessive synthesis of neuronal beta-amyloid precursor protein. In addition, S100Beta induces increases in intraneuronal free calcium concentrations that are neuronotoxic. The resulting neuronal injury can further activate microglia, with further overexpression of interleukin-1, and thereby produce feedback amplification and self-propagation of neurodegenerative processes. Unremitting self-propagation thus provides an explanation for progression of the neurodegenerative changes culminating in Aizheimer's disease.