Clinical use of the inhalation anaesthetic halothane is associated with a rare, but often fatal hepatitis, which is apparently immune-mediated. In recent years, the mechanism of the disease has been shown to involve an antibody response against a specific set of liver proteins that are covalently modified by the reactive trifluoroacetyl chloride metabolite of halothane. This project has focussed on the isolation and characterization of the 1OO kDa protein, to which the majority of patients produce antibodies. The antigen was identified as endoplasmin, a highly conserved glycoprotein with a probable role in calcium homeostasis and intracellular protein transport. In cell culture, we established that the expression of endoplasmin can be induced by hyperphysiologic temperatures. The significance of this finding stems from the emerging role of so-called "heat-shock" stress proteins in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus and in immunity against certain chemically induced tumors. These findings suggest that stress proteins may also have an underlying role in drug allergic reactions.