Alzheimer's disease is probably a complex disease caused by an interaction of multiple environmental and genetic factors. Genetic defects include 'causative' genes which are rare and a 'susceptibility' gene (sigma4 allele of apolipoprotein E) which is more common in cases. Recent research suggests that environmental factors may interact with a genetic predisposition to modify the risk of Alzheimer's disease. An interaction between serum cholesterol levels and sigma4 genotype is proposed. The evidence for this gene-environment interaction is discussed.