Prokaryotes and eukaryotes respond to development cues or cellular challenges by directing their protein synthetic apparatus toward the production of stress proteins. The first expression of these proteins was noted morphologically in the salivary gland polytene chromosomes of Drosophilia melanogaster}1 Ritossa first observed that either shifting the temperature from 20°C to 37°C, or treatments with sodium salicylate or dinitrophenol, produced new chromosome puffing patterns. Tissieres et al., 3 10 years later, showed that heat shock induced the production of a unique set of proteins. Thus, it soon became evident that the puffs observed at the light microscopic level in Drosophila were sites of exuberant RNA transcription, and that the exposure of cells from a wide variety of species to heat challenges produced enhanced synthesis of several unique proteins that were designated heat shock proteins (hsps). In spite of the expression of these proteins following chemical treatment, first described in 1962, this phenomenon has been called the heat shock response. With increased advances in our understanding of the nature of these proteins, including the evidence that they are induced by a wide variety of stresses and that the expression of some of these is refractive to heat shock, there is a trend to refer more appropriately to hsps as stress proteins and the response as the stress response. The heat shock or stress response is probably the most highly conserved genetic system uncovered to date.4 Induction of hsps has been observed in every organism investigated and includes bacteria, soybeans, maize, tobacco, yeast, and many eukaryotes ranging from Drosophila through nematodes, to rat, mouse, and man. The universality of this response and the high level of conservation of these proteins has allowed scientists to investigate the nature and function of hsps in prokaryotes and lower species and then to extrapolate these findings to eukaryotes and higher species. Several advances have expanded our understanding of the stress response and the implications of this phenomenon on the control of normal growth, development, and disease are beginning to emerge. One of the most important advances has been the discovery of mutations of heat shock genes in Saccharomyces cerevisiae and in Escherichia coli. Genetic and molecular analyses of these mutations have permitted investigation of the mechanisms controlling the regulation, expression, and function of stress proteins. Also, polyclonal and monoclonal antibodies directed against hsps have been used to identify the subcellular distribution of these proteins under normal conditions, as well as following incidences of stress, disease, and during development. Finally, many genes of these protein families have been cloned, and promoter sequences necessary for their induction have been discerned in prokaryotes and eukaroytes. In this review we primarily examine some of the hsps that have been studied in mammalian cells. The aim of this review is to begin to draw attention to the role and association between hsps, stress proteins, and their expression during normal development and disease. The reader may also refer to the scholarly reviews of Craig 4 and Lindquist and Craig5 for a comprehensive biochemical and genetic overview of hsps and the heat shock response in prokaryotes and eukaryotes.