Heat and other acute or chronic stresses provoke multiple cellular reactions, including activation of the heat shock or stress protein response. To date, no compounds have become available that specifically activate, or block activation of, the stress protein response. At the transcriptional level the response is mediated by heat shock factors, ubiquitously expressed transcription factors that are normally inactive but are activated in a cell experiencing a stress. Mutant heat shock factors that activate the stress protein response in the absence of a stress or that prevent stress activation of the response have proven useful for studying biological questions associated with a normal or abnormal stress protein response and have been incorporated in the design of gene switches with desirable new properties.