Organisms respond to elevated temperatures and to chemical and physiological stresses by an increase in the synthesis of heat shock proteins. The regulation of heat shock gene expression in eukaryotes is mediated by the conserved heat shock transcription factor (HSF). HSF is present in a latent state under normal conditions; it is activated upon heat stress by induction of trimerization and high-affinity binding to DNA and by exposure of domains for transcriptional activity. Analysis of HSF cDNA clones from many species has defined structural and regulatory regions responsible for the inducible activities. The heat stress signal is thought to be transduced to HSF by changes in the physical environment, in the activity of HSF-modifying enzymes. or by changes in the intracellular level of heat shock proteins.