We have engineered C. elegans to express human beta amyloid peptide, which is believed to be central to Alzheimer disease pathology. This expression has clear pathological effects on these transgenic animals. Characterisation of transgenic animals expressing wild-type or variant beta amyloid peptide indicates that these physiological effects are due to a specific, intrinsic toxicity of the beta amyloid peptide, and not due to non-specific results of foreign protein expression. We have therefore employed microarray hybridisation to examine gene expression changes resulting from beta amyloid expression in this model system, in hopes of understanding the cellular and molecular basis of beta amyloid toxicity. Our initial analysis of two independent beta amyloid/control transgenic pairs, using arrays with 11,990 gene-specific probes, has identified approximately 40 genes that appeared to up-regulated twofold or more in both experiments. Encouragingly, prominent among this set are genes encoding small heat shock proteins, which we have previously demonstrated to be strongly up-regulated in response to beta amyloid peptide expression. We have also initiated microarray analysis of transgenic animals containing suppresser mutations that block phenotypes resulting from beta amyloid expression. Further expression comparisons will serve to refine this list of candidate beta amyloid-responsive genes, which will be subsequently explored in mammalian systems.